http://informahealthcare.com/rst ISSN: 1079-9893 (print), 1532-4281 (electronic) J Recept Signal Transduct Res, 2015; 35(1): 94–97 ! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/10799893.2014.936458
RESEARCH ARTICLE
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by University of Otago on 07/29/15 For personal use only.
Association of monocyte chemoattractant protein-1 2518G/A gene polymorphism with diabetic nephropathy risk Ning Su1*, Hong-Yan Li2*, Miao-Fang Huang1, Zong-Pei Jiang1, and Tian-Biao Zhou1 1
Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China and 2Center of Kidney Disease, Huadu District People’s Hospital, Southern Medical University, Guangzhou, China Abstract
Keywords
Results from the published studies on the association between monocyte chemoattractant protein-1 (MCP-1) 2518 A/G gene polymorphism and diabetic nephropathy (DN) risk are still conflicting. This meta-analysis was performed to evaluate the relationship between MCP-1 A/G gene polymorphism and DN risk and to explore whether MCP-1 A allele, AA genotype or GG genotype could become a predictive marker for DN risk. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of 1 March 2014, and eligible investigations were synthesized using meta-analysis method. Four studies were identified for the analysis of association between MCP-1 A/G gene polymorphism and DN risk, and all the included studies were form Asian population. The association between MCP-1 A/G gene polymorphism and DN susceptibility was not found (A allele: OR ¼ 1.19; 95% CI: 0.97–1.45; p ¼ 0.10; AA genotype: OR ¼ 1.27; 95% CI: 0.95–1.70; p ¼ 0.11; GG genotype: OR ¼ 0.77; 95% CI: 0.57–1.05; p ¼ 0.10). In the sensitive analysis, according to the control source from hospital, we found that AA genotype was associated with the DN risk (OR ¼ 1.45; 95% CI: 1.05–2.00; p ¼ 0.02). However, other associations were not found in the sensitive analysis according to the control source from hospital or population. Our results indicate that AA homozygous might be a significant genetic molecular marker to predict the diabetes mellitus patients developing into DN. However, more investigations are required to further clarify this association.
A/G gene polymorphism, diabetes mellitus, diabetic nephropathy, monocyte chemoattractant protein-1, meta-analysis
Introduction Diabetic nephropathy (DN), one of the leading causes of endstage renal failure, is an important microvascular complication of diabetes mellitus (DM), which is also associated with the increased morbidity and mortality among diabetic patients (1,2). Genetic and environmental factors contribute to the development of DN, and DN is a severe manifestation of DM that exhibits familial aggregation and may progress to endstage renal disease, and it remains a predominant cause of morbidity and mortality in DM. At present, some studies have reported that gene polymorphism was associated with the risk of DN susceptibility (3–5). Monocyte chemoattractant protein-1 (MCP-1) is a member of the C–C family chemokines and an important signal pathway chemokine responsible for the initiation, regulation and mobilization of monocytes to the active sites of severe
History Received 1 May 2014 Revised 31 May 2014 Accepted 11 June 2014 Published online 22 July 2014
periodontal inflammation (6,7). MCP-1 is up regulated in kidney diseases, and it is considered a marker of kidney inflammation (8). Recently, the evidence has indicated that serum levels and biological activity of the MCP-1 protein may be regulated by a single nucleotide polymorphism occurring at position 2518 of the MCP-1 gene promoter (rs1024611) (9). The MCP-1 A/G gene polymorphism might be implicated in the etiology of DN and has been investigated in numerous epidemiologic studies. However, the available evidence is weak at present, due to sparseness of data or disagreements among the reported investigations. The evidence from metaanalysis may be powerful when compared with the individual investigation. In previous, there was no any meta-analysis to assess this association. In this meta-analysis, we searched the published literatures on the relationship between MCP-1 2518 A/G gene polymorphism and DN widely.
Materials and methods *These authors contributed equally to this work. Address for correspondence: Zong-Pei Jiang and Tian-Biao Zhou, Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510655, China. E-mail: [email protected] (Z.-P. Jiang); [email protected] (T.-B. Zhou)
Search strategy for the association of MCP-1 A/G gene polymorphism with DN risk The relevant studies were searched from the electronic databases of PubMed, Embase, Cochrane Library and
MCP-1 with DN
DOI: 10.3109/10799893.2014.936458
95
Table 1. Characteristics of the studies evaluating the effects of MCP-1 2518 A/G gene polymorphism on DN risk.
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by University of Otago on 07/29/15 For personal use only.
SLE
Control
Author, Year
Ethnicity
Country/ district
Source of control
AA
AG
GG
Total
AA
AG
GG
Total
Joo, 2007 Moon, 2007
Asian Asian
Korea Korea
Karadeniz, 2010
Asian
Turkey
65 35 35 0 0
23 41 11 49 17 50
68 87 51 12 0
Korea
164 112 112 43 43 161
78 102 50 44 26
Asian
26 16 16 24 24 28
73 61 61 19 19
Jeon, 2013
Hospital Population Hospital Population Hospital Hospital
169 230 112 105 43 399
CBM-disc (China Biological Medicine Database) on 1 March 2014. The retrieval strategy of (diabetic nephropathy OR DN) AND (monocyte chemoattractant protein-1 OR MCP-1) was entered into these databases mentioned above for search. Additional articles were identified through references cited in retrieved articles. Inclusion and exclusion criteria Inclusion criteria (i) The outcome had to be DN, (ii) there had to be at least two comparison groups (DN group versus control group) and (iii) investigation should provide the detailed data of MCP-1 genotype distribution. Exclusion criteria (i) Review articles and editorials, (ii) case reports, (iii) preliminary result not on MCP-1 A/G gene polymorphism or outcome, (iv) Investigating the role MCP-1 to disease and (v) if multiple publications from the same study group occurred, we only recruited the most complete paper into our final analysis. Data extraction and synthesis Two investigators independently extracted the following information from each eligible study: first author’s surname, year of publication and the number of cases and controls for MCP-1 genotypes. Frequency of A allele was calculated for case group and control group, from the corresponding genotype distribution. The results were compared and disagreement was resolved by discussion. Statistical analysis Cochrane Review Manager Version 5 (Cochrane Library, UK) was used to calculate the available data from each investigation. The pooled statistic was counted using the fixed effects model, but a random effects model was conducted when the p value of heterogeneity test was 50.1. Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CIs) were also calculated. p50.05 was required for the pooled OR to be statistically significant. I2 was used to test the heterogeneity among the included studies. The sensitive analysis according to the control source from hospital or population was also performed in this meta-analysis.
Results Search results for the association of MCP-1 A/G gene polymorphism with DN risk After carefully applying the inclusion and exclusion criteria, four studies (10–13) were identified as suitable for inclusion in the meta-analysis on the association between the MCP-1 A/G gene polymorphism and DN susceptibility, and all the included studies were from Asian population (Table 1). Association of MCP-1 A/G gene polymorphism with DN risk In this meta-analysis, we found that A allele, AA genotype and GG genotype were not associated with DN risk (A allele: OR ¼ 1.19; 95% CI: 0.97–1.45; p ¼ 0.10; AA genotype: OR ¼ 1.27; 95% CI: 0.95–1.70; p ¼ 0.11; GG genotype: OR ¼ 0.77; 95% CI: 0.57–1.05; p ¼ 0.10; Figure 1 and Table 2). Sensitive analysis Sensitive analysis was also performed in this study. When the studies with the control group from healthy population were included for meta-analysis, we found that A allele, AA genotype and GG genotype were not associated with DN risk (A allele: OR ¼ 1.19; 95% CI: 0.90–1.58; p ¼ 0.22; AA genotype: OR ¼ 1.01; 95% CI: 0.63–1.60; p ¼ 0.98; GG genotype: OR ¼ 0.30; 95% CI: 0.02–3.74; p ¼ 0.35; Table 2). When the studies with the control group from hospital population were included for meta-analysis, we found that AA genotype was associated with the risk of DN (OR ¼ 1.45; 95% CI: 1.05–2.00; p ¼ 0.02; Table 2), but the A allele and GG genotype were not (A allele: OR ¼ 1.25; 95% CI: 0.99–1.57; p ¼ 0.06; GG genotype: OR ¼ 0.77; 95% CI: 0.55–1.09; p ¼ 0.14; Table 2).
Discussion The results from this meta-analysis indicated that MCP-1 A/G gene polymorphism could not predict the onset of DN. When the sensitivity analysis according to control from hospital was performed, we found that AA genotype was associated with the risk of DN, but the A allele and GG genotype were not. The patients in the control from hospital were sourced from DM. So, our results indicate that AA homozygous might be a significant genetic molecular marker to predict the DM patients developing into DN. However, this
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by University of Otago on 07/29/15 For personal use only.
96
N. Su et al.
J Recept Signal Transduct Res, 2015; 35(1): 94–97
Figure 1. Association of MCP-1 2518 A/G gene polymorphism with DN susceptibility.
Table 2. Meta analysis of the association of MCP-1 2518 A/G gene polymorphism with risk of DN.
Genetic contrasts A versus G
AA versus (AG + GG)
GG versus (AG + AA)
Group and subgroups
Studies
Q test p value
Model selected
Overall Population Hospital Overall Population Hospital Overall Population Hospital
3 2 3 4 2 4 3 2 3
0.42 0.18 0.33 0.63 0.19 0.84 0.22 0.07 0.10
Fixed Fixed Fixed Fixed Fixed Fixed Fixed Random Fixed
conclusion should be confirmed by larger sample size and well designed study in the future. In the recruited studies, Joo et al. (10) included 177 diabetic end-stage renal disease (ESRD) patients and 184 patients without renal involvement (controls) in order to investigate the effects of MCP-1 on DN in Korean patients with type 2 DM, and reported the gene distribution between two groups were not different. Moon et al. (11) investigated 2518 A/G polymorphism of the MCP-1 gene in type 2 DM patients with progressive kidney failure (n ¼ 112) compared with matched type 2 DM patients without nephropathy
OR (95% CI) 1.19 1.19 1.25 1.27 1.01 1.45 0.77 0.30 0.77
(0.97, (0.90, (0.99, (0.95, (0.63, (1.05, (0.57, (0.02, (0.55,
1.45) 1.58) 1.57) 1.70) 1.60) 2.00) 1.05) 3.74) 1.09)
p Value 0.10 0.22 0.06 0.11 0.98 0.02 0.10 0.35 0.14
(diabetic control, n ¼ 112) and healthy controls (n ¼ 230), and A allele was more frequent in patients with kidney failure than in DM controls. Karadeniz et al. (12) investigated genotypic and allelic frequencies of MCP-1 gene polymorphism in the healthy and patients with and without DN, and their results indicated that the genotype MCP-1 (2518G/A) distribution did differ between the control group and the type 2 diabetic patients, and the AA genotype or A allele at MCP-1 2518 was an independent risk factor for the progression of type 2 diabetes. Jeon et al. (13) conducted a case–control study, which enrolled 590 subjects with type 2
MCP-1 with DN
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by University of Otago on 07/29/15 For personal use only.
DOI: 10.3109/10799893.2014.936458
diabetes, and found that the prevalence of nephropathy event was not different according to the 2518A/G genotypes. To sum up those mentioned above, our results indicated that, in the sensitive analysis according to the control source from hospital, AA genotype was associated with the DN risk and AA homozygous might be a significant genetic molecular marker to predict the DM patients developing into DN. The outcome should be confirmed in the future. However, those findings should be regarded cautiously because many other ingredients, such as language bias, small sample size of the included report, limited statistical power, heterogeneity of enrolled cases, variable study designs and different interventions, were closely related to affect the results. In conclusion, the results from our study supported that the association between MCP-1 A/G gene polymorphism and DN susceptibility was not found. However, AA homozygous might be a significant genetic molecular marker to predict the DM patients developing into DN. More association investigations with larger sample size are required to further clarify the role of the MCP-1 A/G gene polymorphism in predicting the risk of DN.
3.
4.
5.
6.
7.
8. 9.
10.
Declaration of interest The authors declare no competing interests. This study was supported by the sub-item of 985 Project Foundation of Sun Yat-Sen (The Hundred Talents Program Foundation; No. 88000-3311300) and by Guangzhou medical key subject construction project.
11.
12.
References 1. Kong LL, Wu H, Cui WP, et al. Advances in murine models of diabetic nephropathy. J Diabetes Res 2013;2013:797548. 2. Zhou TB, Jiang ZP, Qin YH, et al. Association of transforming growth factor-beta1 T869C gene polymorphism
13.
97
with diabetic nephropathy risk. Nephrology (Carlton) 2014;19: 107–15. Yu ZY, Chen LS, Zhang LC, et al. Meta-analysis of the relationship between ACE I/D gene polymorphism and end-stage renal disease in patients with diabetic nephropathy. Nephrology (Carlton) 2012; 17:480–7. Zhou TB, Guo XF, Yin SS. Association of peroxisome proliferatoractivated receptor gamma Pro12Ala gene polymorphism with type 2 diabetic nephropathy risk in Caucasian population. J Recept Signal Transduct Res 2014;34:180–4. Zhou TB, Xu HL, Yin SS. Association between endothelial nitric oxide synthase Glu298Asp gene polymorphism and diabetic nephropathy susceptibility. Ren Fail 2013;35:173–8. Gupta M, Chaturvedi R, Jain A. Role of monocyte chemoattractant protein-1 (MCP-1) as an immune-diagnostic biomarker in the pathogenesis of chronic periodontal disease. Cytokine 2013;61: 892–7. Ishioka K, Suzuki Y, Tajima K, et al. Monocyte chemoattractant protein-1 in dogs affected with neoplasia or inflammation. J Vet Med Sci 2013;75:173–7. Tofik R, Ohlsson S, Bakoush O. Urinary concentration of monocyte chemoattractant protein-1 in idiopathic glomerulonephritis: a longterm follow-up study. PLoS One 2014;9:e87857. Pola R, Flex A, Gaetani E, et al. Monocyte chemoattractant protein1 (MCP-1) gene polymorphism and risk of Alzheimer’s disease in Italians. Exp Gerontol 2004;39:1249–52. Joo KW, Hwang YH, Kim JH, et al. MCP-1 and RANTES polymorphisms in Korean diabetic end-stage renal disease. J Korean Med Sci 2007;22:611–15. Moon JY, Jeong L, Lee S, et al. Association of polymorphisms in monocyte chemoattractant protein-1 promoter with diabetic kidney failure in Korean patients with type 2 diabetes mellitus. J Korean Med Sci 2007;22:810–14. Karadeniz M, Erdogan M, Cetinkalp S, et al. Monocyte chemoattractant protein-1 (MCP-1) 2518G/A gene polymorphism in Turkish type 2 diabetes patients with nephropathy. Endocrine 2010; 37:513–17. Jeon HJ, Choi HJ, Park BH, et al. Association of monocyte chemoattractant protein-1 (MCP-1) 2518A/G polymorphism with proliferative diabetic retinopathy in Korean type 2 diabetes. Yonsei Med J 2013;54:621–5.
RESEARCH ARTICLE
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by University of Otago on 07/29/15 For personal use only.
Association of monocyte chemoattractant protein-1 2518G/A gene polymorphism with diabetic nephropathy risk Ning Su1*, Hong-Yan Li2*, Miao-Fang Huang1, Zong-Pei Jiang1, and Tian-Biao Zhou1 1
Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China and 2Center of Kidney Disease, Huadu District People’s Hospital, Southern Medical University, Guangzhou, China Abstract
Keywords
Results from the published studies on the association between monocyte chemoattractant protein-1 (MCP-1) 2518 A/G gene polymorphism and diabetic nephropathy (DN) risk are still conflicting. This meta-analysis was performed to evaluate the relationship between MCP-1 A/G gene polymorphism and DN risk and to explore whether MCP-1 A allele, AA genotype or GG genotype could become a predictive marker for DN risk. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of 1 March 2014, and eligible investigations were synthesized using meta-analysis method. Four studies were identified for the analysis of association between MCP-1 A/G gene polymorphism and DN risk, and all the included studies were form Asian population. The association between MCP-1 A/G gene polymorphism and DN susceptibility was not found (A allele: OR ¼ 1.19; 95% CI: 0.97–1.45; p ¼ 0.10; AA genotype: OR ¼ 1.27; 95% CI: 0.95–1.70; p ¼ 0.11; GG genotype: OR ¼ 0.77; 95% CI: 0.57–1.05; p ¼ 0.10). In the sensitive analysis, according to the control source from hospital, we found that AA genotype was associated with the DN risk (OR ¼ 1.45; 95% CI: 1.05–2.00; p ¼ 0.02). However, other associations were not found in the sensitive analysis according to the control source from hospital or population. Our results indicate that AA homozygous might be a significant genetic molecular marker to predict the diabetes mellitus patients developing into DN. However, more investigations are required to further clarify this association.
A/G gene polymorphism, diabetes mellitus, diabetic nephropathy, monocyte chemoattractant protein-1, meta-analysis
Introduction Diabetic nephropathy (DN), one of the leading causes of endstage renal failure, is an important microvascular complication of diabetes mellitus (DM), which is also associated with the increased morbidity and mortality among diabetic patients (1,2). Genetic and environmental factors contribute to the development of DN, and DN is a severe manifestation of DM that exhibits familial aggregation and may progress to endstage renal disease, and it remains a predominant cause of morbidity and mortality in DM. At present, some studies have reported that gene polymorphism was associated with the risk of DN susceptibility (3–5). Monocyte chemoattractant protein-1 (MCP-1) is a member of the C–C family chemokines and an important signal pathway chemokine responsible for the initiation, regulation and mobilization of monocytes to the active sites of severe
History Received 1 May 2014 Revised 31 May 2014 Accepted 11 June 2014 Published online 22 July 2014
periodontal inflammation (6,7). MCP-1 is up regulated in kidney diseases, and it is considered a marker of kidney inflammation (8). Recently, the evidence has indicated that serum levels and biological activity of the MCP-1 protein may be regulated by a single nucleotide polymorphism occurring at position 2518 of the MCP-1 gene promoter (rs1024611) (9). The MCP-1 A/G gene polymorphism might be implicated in the etiology of DN and has been investigated in numerous epidemiologic studies. However, the available evidence is weak at present, due to sparseness of data or disagreements among the reported investigations. The evidence from metaanalysis may be powerful when compared with the individual investigation. In previous, there was no any meta-analysis to assess this association. In this meta-analysis, we searched the published literatures on the relationship between MCP-1 2518 A/G gene polymorphism and DN widely.
Materials and methods *These authors contributed equally to this work. Address for correspondence: Zong-Pei Jiang and Tian-Biao Zhou, Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510655, China. E-mail: [email protected] (Z.-P. Jiang); [email protected] (T.-B. Zhou)
Search strategy for the association of MCP-1 A/G gene polymorphism with DN risk The relevant studies were searched from the electronic databases of PubMed, Embase, Cochrane Library and
MCP-1 with DN
DOI: 10.3109/10799893.2014.936458
95
Table 1. Characteristics of the studies evaluating the effects of MCP-1 2518 A/G gene polymorphism on DN risk.
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by University of Otago on 07/29/15 For personal use only.
SLE
Control
Author, Year
Ethnicity
Country/ district
Source of control
AA
AG
GG
Total
AA
AG
GG
Total
Joo, 2007 Moon, 2007
Asian Asian
Korea Korea
Karadeniz, 2010
Asian
Turkey
65 35 35 0 0
23 41 11 49 17 50
68 87 51 12 0
Korea
164 112 112 43 43 161
78 102 50 44 26
Asian
26 16 16 24 24 28
73 61 61 19 19
Jeon, 2013
Hospital Population Hospital Population Hospital Hospital
169 230 112 105 43 399
CBM-disc (China Biological Medicine Database) on 1 March 2014. The retrieval strategy of (diabetic nephropathy OR DN) AND (monocyte chemoattractant protein-1 OR MCP-1) was entered into these databases mentioned above for search. Additional articles were identified through references cited in retrieved articles. Inclusion and exclusion criteria Inclusion criteria (i) The outcome had to be DN, (ii) there had to be at least two comparison groups (DN group versus control group) and (iii) investigation should provide the detailed data of MCP-1 genotype distribution. Exclusion criteria (i) Review articles and editorials, (ii) case reports, (iii) preliminary result not on MCP-1 A/G gene polymorphism or outcome, (iv) Investigating the role MCP-1 to disease and (v) if multiple publications from the same study group occurred, we only recruited the most complete paper into our final analysis. Data extraction and synthesis Two investigators independently extracted the following information from each eligible study: first author’s surname, year of publication and the number of cases and controls for MCP-1 genotypes. Frequency of A allele was calculated for case group and control group, from the corresponding genotype distribution. The results were compared and disagreement was resolved by discussion. Statistical analysis Cochrane Review Manager Version 5 (Cochrane Library, UK) was used to calculate the available data from each investigation. The pooled statistic was counted using the fixed effects model, but a random effects model was conducted when the p value of heterogeneity test was 50.1. Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CIs) were also calculated. p50.05 was required for the pooled OR to be statistically significant. I2 was used to test the heterogeneity among the included studies. The sensitive analysis according to the control source from hospital or population was also performed in this meta-analysis.
Results Search results for the association of MCP-1 A/G gene polymorphism with DN risk After carefully applying the inclusion and exclusion criteria, four studies (10–13) were identified as suitable for inclusion in the meta-analysis on the association between the MCP-1 A/G gene polymorphism and DN susceptibility, and all the included studies were from Asian population (Table 1). Association of MCP-1 A/G gene polymorphism with DN risk In this meta-analysis, we found that A allele, AA genotype and GG genotype were not associated with DN risk (A allele: OR ¼ 1.19; 95% CI: 0.97–1.45; p ¼ 0.10; AA genotype: OR ¼ 1.27; 95% CI: 0.95–1.70; p ¼ 0.11; GG genotype: OR ¼ 0.77; 95% CI: 0.57–1.05; p ¼ 0.10; Figure 1 and Table 2). Sensitive analysis Sensitive analysis was also performed in this study. When the studies with the control group from healthy population were included for meta-analysis, we found that A allele, AA genotype and GG genotype were not associated with DN risk (A allele: OR ¼ 1.19; 95% CI: 0.90–1.58; p ¼ 0.22; AA genotype: OR ¼ 1.01; 95% CI: 0.63–1.60; p ¼ 0.98; GG genotype: OR ¼ 0.30; 95% CI: 0.02–3.74; p ¼ 0.35; Table 2). When the studies with the control group from hospital population were included for meta-analysis, we found that AA genotype was associated with the risk of DN (OR ¼ 1.45; 95% CI: 1.05–2.00; p ¼ 0.02; Table 2), but the A allele and GG genotype were not (A allele: OR ¼ 1.25; 95% CI: 0.99–1.57; p ¼ 0.06; GG genotype: OR ¼ 0.77; 95% CI: 0.55–1.09; p ¼ 0.14; Table 2).
Discussion The results from this meta-analysis indicated that MCP-1 A/G gene polymorphism could not predict the onset of DN. When the sensitivity analysis according to control from hospital was performed, we found that AA genotype was associated with the risk of DN, but the A allele and GG genotype were not. The patients in the control from hospital were sourced from DM. So, our results indicate that AA homozygous might be a significant genetic molecular marker to predict the DM patients developing into DN. However, this
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by University of Otago on 07/29/15 For personal use only.
96
N. Su et al.
J Recept Signal Transduct Res, 2015; 35(1): 94–97
Figure 1. Association of MCP-1 2518 A/G gene polymorphism with DN susceptibility.
Table 2. Meta analysis of the association of MCP-1 2518 A/G gene polymorphism with risk of DN.
Genetic contrasts A versus G
AA versus (AG + GG)
GG versus (AG + AA)
Group and subgroups
Studies
Q test p value
Model selected
Overall Population Hospital Overall Population Hospital Overall Population Hospital
3 2 3 4 2 4 3 2 3
0.42 0.18 0.33 0.63 0.19 0.84 0.22 0.07 0.10
Fixed Fixed Fixed Fixed Fixed Fixed Fixed Random Fixed
conclusion should be confirmed by larger sample size and well designed study in the future. In the recruited studies, Joo et al. (10) included 177 diabetic end-stage renal disease (ESRD) patients and 184 patients without renal involvement (controls) in order to investigate the effects of MCP-1 on DN in Korean patients with type 2 DM, and reported the gene distribution between two groups were not different. Moon et al. (11) investigated 2518 A/G polymorphism of the MCP-1 gene in type 2 DM patients with progressive kidney failure (n ¼ 112) compared with matched type 2 DM patients without nephropathy
OR (95% CI) 1.19 1.19 1.25 1.27 1.01 1.45 0.77 0.30 0.77
(0.97, (0.90, (0.99, (0.95, (0.63, (1.05, (0.57, (0.02, (0.55,
1.45) 1.58) 1.57) 1.70) 1.60) 2.00) 1.05) 3.74) 1.09)
p Value 0.10 0.22 0.06 0.11 0.98 0.02 0.10 0.35 0.14
(diabetic control, n ¼ 112) and healthy controls (n ¼ 230), and A allele was more frequent in patients with kidney failure than in DM controls. Karadeniz et al. (12) investigated genotypic and allelic frequencies of MCP-1 gene polymorphism in the healthy and patients with and without DN, and their results indicated that the genotype MCP-1 (2518G/A) distribution did differ between the control group and the type 2 diabetic patients, and the AA genotype or A allele at MCP-1 2518 was an independent risk factor for the progression of type 2 diabetes. Jeon et al. (13) conducted a case–control study, which enrolled 590 subjects with type 2
MCP-1 with DN
Journal of Receptors and Signal Transduction Downloaded from informahealthcare.com by University of Otago on 07/29/15 For personal use only.
DOI: 10.3109/10799893.2014.936458
diabetes, and found that the prevalence of nephropathy event was not different according to the 2518A/G genotypes. To sum up those mentioned above, our results indicated that, in the sensitive analysis according to the control source from hospital, AA genotype was associated with the DN risk and AA homozygous might be a significant genetic molecular marker to predict the DM patients developing into DN. The outcome should be confirmed in the future. However, those findings should be regarded cautiously because many other ingredients, such as language bias, small sample size of the included report, limited statistical power, heterogeneity of enrolled cases, variable study designs and different interventions, were closely related to affect the results. In conclusion, the results from our study supported that the association between MCP-1 A/G gene polymorphism and DN susceptibility was not found. However, AA homozygous might be a significant genetic molecular marker to predict the DM patients developing into DN. More association investigations with larger sample size are required to further clarify the role of the MCP-1 A/G gene polymorphism in predicting the risk of DN.
3.
4.
5.
6.
7.
8. 9.
10.
Declaration of interest The authors declare no competing interests. This study was supported by the sub-item of 985 Project Foundation of Sun Yat-Sen (The Hundred Talents Program Foundation; No. 88000-3311300) and by Guangzhou medical key subject construction project.
11.
12.
References 1. Kong LL, Wu H, Cui WP, et al. Advances in murine models of diabetic nephropathy. J Diabetes Res 2013;2013:797548. 2. Zhou TB, Jiang ZP, Qin YH, et al. Association of transforming growth factor-beta1 T869C gene polymorphism
13.
97
with diabetic nephropathy risk. Nephrology (Carlton) 2014;19: 107–15. Yu ZY, Chen LS, Zhang LC, et al. Meta-analysis of the relationship between ACE I/D gene polymorphism and end-stage renal disease in patients with diabetic nephropathy. Nephrology (Carlton) 2012; 17:480–7. Zhou TB, Guo XF, Yin SS. Association of peroxisome proliferatoractivated receptor gamma Pro12Ala gene polymorphism with type 2 diabetic nephropathy risk in Caucasian population. J Recept Signal Transduct Res 2014;34:180–4. Zhou TB, Xu HL, Yin SS. Association between endothelial nitric oxide synthase Glu298Asp gene polymorphism and diabetic nephropathy susceptibility. Ren Fail 2013;35:173–8. Gupta M, Chaturvedi R, Jain A. Role of monocyte chemoattractant protein-1 (MCP-1) as an immune-diagnostic biomarker in the pathogenesis of chronic periodontal disease. Cytokine 2013;61: 892–7. Ishioka K, Suzuki Y, Tajima K, et al. Monocyte chemoattractant protein-1 in dogs affected with neoplasia or inflammation. J Vet Med Sci 2013;75:173–7. Tofik R, Ohlsson S, Bakoush O. Urinary concentration of monocyte chemoattractant protein-1 in idiopathic glomerulonephritis: a longterm follow-up study. PLoS One 2014;9:e87857. Pola R, Flex A, Gaetani E, et al. Monocyte chemoattractant protein1 (MCP-1) gene polymorphism and risk of Alzheimer’s disease in Italians. Exp Gerontol 2004;39:1249–52. Joo KW, Hwang YH, Kim JH, et al. MCP-1 and RANTES polymorphisms in Korean diabetic end-stage renal disease. J Korean Med Sci 2007;22:611–15. Moon JY, Jeong L, Lee S, et al. Association of polymorphisms in monocyte chemoattractant protein-1 promoter with diabetic kidney failure in Korean patients with type 2 diabetes mellitus. J Korean Med Sci 2007;22:810–14. Karadeniz M, Erdogan M, Cetinkalp S, et al. Monocyte chemoattractant protein-1 (MCP-1) 2518G/A gene polymorphism in Turkish type 2 diabetes patients with nephropathy. Endocrine 2010; 37:513–17. Jeon HJ, Choi HJ, Park BH, et al. Association of monocyte chemoattractant protein-1 (MCP-1) 2518A/G polymorphism with proliferative diabetic retinopathy in Korean type 2 diabetes. Yonsei Med J 2013;54:621–5.
