Original Article Received. January 14, 2015 Accepted: April 6, 2015 Published online: May 13, 2015
Gynecol Obstet Invest DOI: 10.1159/000398796
Association of Macrophage Migration Inhibitory Factor Polymorphisms with Gestational Diabetes Mellitus in Han Chinese Women Chao Li a Binglong Qiao b Weihong Qi a Ying Zhan a Chunling Ma a Lei Zhao a Guiyu Li a
Department of Obstetrics, The Affiliated Hospital of Qingdao University, and b Department of Radiology, Qingdao Municipal Hospital, Qingdao, China
Key Words Macrophage migration inhibitory factor · Polymorphism · Gestational diabetes mellitus
Abstract Objective: The purpose of the study was to investigate the association between macrophage migration inhibitory factor (MIF) gene polymorphisms and gestational diabetes mellitus (GDM) in Han Chinese women. Methods: In this study, 915 unrelated pregnant women were recruited, among whom 430 had GDM and 485 served as controls. The rs755622 in the MIF gene (MIF-173G/C) was detected by the polymerase chain reaction Tm-shift genotyping method with fluorescence melting curve analysis. The associations of rs755622 in MIF variants with plasma glucose and insulin levels in the oral glucose tolerance test (OGTT) as well as with with blood fat levels were investigated. Results: The frequencies of genotypes and allele types of rs755622 in MIF were significantly different between women of the GDM and control groups (all p < 0.001). Moreover, the single nucleotide polymorphism (SNP) was significantly associated with increased glucose levels at 0, 60 and 120 min during the OGTT (all p < 0.0038) and with the increased homeostasis model assessment of insulin resistance (p < 0.001) in the
© 2015 S. Karger AG, Basel 0378–7346/15/0000–0000$39.50/0 E-Mail [email protected] www.karger.com/goi
GDM group. Conclusion: Genetic polymorphism of rs755622 in MIF is associated with increased risk of GDM and insulin resistance in Han Chinese women. © 2015 S. Karger AG, Basel
Introduction
Gestational diabetes mellitus (GDM) is defined as glucose intolerance first recognized during pregnancy, and is characterized by impaired insulin secretion and action [1]. About one woman out of five has a pregnancy complicated by GDM [2]. GDM poses short- and long-term threats to mothers and infants [3, 4]. It is possible to hypothesize that GDM and type 2 diabetes (T2D) may have similar genetic susceptibilities and risk factors [5–7]. In addition, women with prior GDM are at an increased risk of developing T2D later in life [8], and those with a family history of diabetes are predisposed to an increased risk of GDM [9]. In view of the striking similarities between GDM and T2D, it is also likely that GDM is a multigenic disease related to T2D. Accordingly, recent research on the etiology of GDM has focused on evaluating the roles of common variants in genes predisposing to T2D. In addition, immune-regulatory molecules and chronic systemic inflammation Chao Li Department of Obstetrics The Affiliated Hospital of Qingdao University Qingdao (China) E-Mail lichaoqy @ 126.com
Downloaded by: NYU Medical Center Library 128.122.253.212 - 5/20/2015 9:10:42 AM
a
Subjects and Methods Subjects The study was approved by the Affiliated Hospital of Qingdao University Ethics Committee, and informed consent was obtained from all participants. The study participants comprised 915 Han Chinese women residing in Shandong province. Among them, 430 (32.31 ± 4.92 years old) had GDM and 485 (31.96 ± 5.22 years old) were in the normal pregnancy group, with normal glucose tolerance. Pregnant women with pre-existing diabetes and antenatal patients pre-diagnosed with T1D or T2D were excluded from the study. Clinical and biochemical data were collected for all participants at 24–28
2
Gynecol Obstet Invest DOI: 10.1159/000398796
Table 1. Clinical and biochemical parameters of healthy women
and GDM patients Characteristic
Controls
GDM patients
Number Age, years Gestational age, weeks Pre-BMI Glucose, mmol/l OGTT 0 min OGTT 60 min OGTT 120 min Insulin, mIU/l OGTT 0 min OGTT 60 min OGTT 120 min HOMA-IR CH, mmol/l LDL, mmol/l HDL, mmol/l TG, mmol/l
485 31.96 ± 5.22 39.10 ± 1.11
t
p value
430 32.31 ± 4.92 38.97 ± 1.07
1.04 1.80
0.30 0.07
24.78 ± 4.63
25.33 ± 4.97
1.10
0.27
4.72 ± 0.62 8.65 ± 1.41 7.02 ± 1.34
6.13 ± 1.21 12.24 ± 2.41 9.81 ± 2.13
22.54
Gynecol Obstet Invest DOI: 10.1159/000398796
Association of Macrophage Migration Inhibitory Factor Polymorphisms with Gestational Diabetes Mellitus in Han Chinese Women Chao Li a Binglong Qiao b Weihong Qi a Ying Zhan a Chunling Ma a Lei Zhao a Guiyu Li a
Department of Obstetrics, The Affiliated Hospital of Qingdao University, and b Department of Radiology, Qingdao Municipal Hospital, Qingdao, China
Key Words Macrophage migration inhibitory factor · Polymorphism · Gestational diabetes mellitus
Abstract Objective: The purpose of the study was to investigate the association between macrophage migration inhibitory factor (MIF) gene polymorphisms and gestational diabetes mellitus (GDM) in Han Chinese women. Methods: In this study, 915 unrelated pregnant women were recruited, among whom 430 had GDM and 485 served as controls. The rs755622 in the MIF gene (MIF-173G/C) was detected by the polymerase chain reaction Tm-shift genotyping method with fluorescence melting curve analysis. The associations of rs755622 in MIF variants with plasma glucose and insulin levels in the oral glucose tolerance test (OGTT) as well as with with blood fat levels were investigated. Results: The frequencies of genotypes and allele types of rs755622 in MIF were significantly different between women of the GDM and control groups (all p < 0.001). Moreover, the single nucleotide polymorphism (SNP) was significantly associated with increased glucose levels at 0, 60 and 120 min during the OGTT (all p < 0.0038) and with the increased homeostasis model assessment of insulin resistance (p < 0.001) in the
© 2015 S. Karger AG, Basel 0378–7346/15/0000–0000$39.50/0 E-Mail [email protected] www.karger.com/goi
GDM group. Conclusion: Genetic polymorphism of rs755622 in MIF is associated with increased risk of GDM and insulin resistance in Han Chinese women. © 2015 S. Karger AG, Basel
Introduction
Gestational diabetes mellitus (GDM) is defined as glucose intolerance first recognized during pregnancy, and is characterized by impaired insulin secretion and action [1]. About one woman out of five has a pregnancy complicated by GDM [2]. GDM poses short- and long-term threats to mothers and infants [3, 4]. It is possible to hypothesize that GDM and type 2 diabetes (T2D) may have similar genetic susceptibilities and risk factors [5–7]. In addition, women with prior GDM are at an increased risk of developing T2D later in life [8], and those with a family history of diabetes are predisposed to an increased risk of GDM [9]. In view of the striking similarities between GDM and T2D, it is also likely that GDM is a multigenic disease related to T2D. Accordingly, recent research on the etiology of GDM has focused on evaluating the roles of common variants in genes predisposing to T2D. In addition, immune-regulatory molecules and chronic systemic inflammation Chao Li Department of Obstetrics The Affiliated Hospital of Qingdao University Qingdao (China) E-Mail lichaoqy @ 126.com
Downloaded by: NYU Medical Center Library 128.122.253.212 - 5/20/2015 9:10:42 AM
a
Subjects and Methods Subjects The study was approved by the Affiliated Hospital of Qingdao University Ethics Committee, and informed consent was obtained from all participants. The study participants comprised 915 Han Chinese women residing in Shandong province. Among them, 430 (32.31 ± 4.92 years old) had GDM and 485 (31.96 ± 5.22 years old) were in the normal pregnancy group, with normal glucose tolerance. Pregnant women with pre-existing diabetes and antenatal patients pre-diagnosed with T1D or T2D were excluded from the study. Clinical and biochemical data were collected for all participants at 24–28
2
Gynecol Obstet Invest DOI: 10.1159/000398796
Table 1. Clinical and biochemical parameters of healthy women
and GDM patients Characteristic
Controls
GDM patients
Number Age, years Gestational age, weeks Pre-BMI Glucose, mmol/l OGTT 0 min OGTT 60 min OGTT 120 min Insulin, mIU/l OGTT 0 min OGTT 60 min OGTT 120 min HOMA-IR CH, mmol/l LDL, mmol/l HDL, mmol/l TG, mmol/l
485 31.96 ± 5.22 39.10 ± 1.11
t
p value
430 32.31 ± 4.92 38.97 ± 1.07
1.04 1.80
0.30 0.07
24.78 ± 4.63
25.33 ± 4.97
1.10
0.27
4.72 ± 0.62 8.65 ± 1.41 7.02 ± 1.34
6.13 ± 1.21 12.24 ± 2.41 9.81 ± 2.13
22.54
