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Vol. 179, No. 9 DOI: 10.1093/aje/kwu024 Advance Access publication: March 26, 2014
Human Genome Epidemiology (HuGE) Review Association Between Heme Oxygenase 1 Gene Promoter Polymorphisms and Susceptibility to Coronary Artery Disease: A HuGE Review and Meta-Analysis
Huaiyu Qiao*, Xiaoyong Sai, Luyue Gai, Guoming Huang, Xiaoyan Chen, Xiaowen Tu, and Zhongru Ding
Initially submitted June 8, 2013; accepted for publication January 23, 2014.
We performed a systematic review and meta-analysis of heme oxygenase 1 gene (HO-1) promoter polymorphisms and susceptibility to coronary artery disease (CAD) based on eligible studies retrieved from electronic databases from 2002 to 2013. Eleven studies, involving 10,170 patients with CAD and 6,868 controls, were included. Overall, no significantly decreased risk of CAD was found in persons with the SS genotype of the HO-1 (GT)n repeat length polymorphism compared with those with the LL + SL genotype. However, decreased risks of CAD were observed in the Asian subgroup, the coronary-artery-narrowing ≥50% subgroup, the myocardial infarction subgroup, the age- and sex-matched subgroup, and the good-quality-reports subgroup. The primary heterogeneity in the studies came from age and sex matching and the extent of coronary stenosis. CAD risk was significantly decreased for persons with the AA genotype of the T(-413)A single-nucleotide polymorphism versus those with the TT genotype, but most of the studies showed that the allele distribution was inconsistent with Hardy-Weinberg equilibrium. In this meta-analysis, we found that the (GT)n SS genotype was associated with decreased risk of CAD after controlling for biases due to age and sex matching, extent of coronary stenosis, ethnicity, and study quality. The relationship between the T(-413)A single-nucleotide polymorphism and CAD should be interpreted more cautiously. coronary artery disease; epidemiology; genetics; heme oxygenase 1; HO-1; meta-analysis; polymorphism
Abbreviations: CAD, coronary artery disease; CI, confidence interval; HO-1, heme oxygenase 1; HuGE, Human Genome Epidemiology; OR, odds ratio; SNP, single-nucleotide polymorphism.
Editor’s note: This article also appears on the website of the Human Genome Epidemiology Network (http://www.cdc. gov/genomics/hugenet/default.htm).
(3). The HO-1 gene is located on human chromosome 22 at 22q12 (4). The protein encoded by HO-1 degrades heme to carbon monoxide, bivalent iron cations (Fe2+), and biliverdin, which is then converted to bilirubin by biliverdin reductase (5). As the inducible isoform of heme oxygenase, the HO-1 protein is highly responsive to its substrate, heme, as well as to a broad spectrum of chemical and physical stress agents. Therefore, the induction of HO-1 is considered a biomarker for cell stress (6). Among a panel of described polymorphisms in the HO-1 gene (3, 7, 8), 2 have attracted the most attention: a (GT)n dinucleotide repeat length polymorphism and a common single-nucleotide polymorphism (SNP), T(-413)A (rs2071746). The (GT)n short allele (S,
Vol. 179, No. 9 DOI: 10.1093/aje/kwu024 Advance Access publication: March 26, 2014
Human Genome Epidemiology (HuGE) Review Association Between Heme Oxygenase 1 Gene Promoter Polymorphisms and Susceptibility to Coronary Artery Disease: A HuGE Review and Meta-Analysis
Huaiyu Qiao*, Xiaoyong Sai, Luyue Gai, Guoming Huang, Xiaoyan Chen, Xiaowen Tu, and Zhongru Ding
Initially submitted June 8, 2013; accepted for publication January 23, 2014.
We performed a systematic review and meta-analysis of heme oxygenase 1 gene (HO-1) promoter polymorphisms and susceptibility to coronary artery disease (CAD) based on eligible studies retrieved from electronic databases from 2002 to 2013. Eleven studies, involving 10,170 patients with CAD and 6,868 controls, were included. Overall, no significantly decreased risk of CAD was found in persons with the SS genotype of the HO-1 (GT)n repeat length polymorphism compared with those with the LL + SL genotype. However, decreased risks of CAD were observed in the Asian subgroup, the coronary-artery-narrowing ≥50% subgroup, the myocardial infarction subgroup, the age- and sex-matched subgroup, and the good-quality-reports subgroup. The primary heterogeneity in the studies came from age and sex matching and the extent of coronary stenosis. CAD risk was significantly decreased for persons with the AA genotype of the T(-413)A single-nucleotide polymorphism versus those with the TT genotype, but most of the studies showed that the allele distribution was inconsistent with Hardy-Weinberg equilibrium. In this meta-analysis, we found that the (GT)n SS genotype was associated with decreased risk of CAD after controlling for biases due to age and sex matching, extent of coronary stenosis, ethnicity, and study quality. The relationship between the T(-413)A single-nucleotide polymorphism and CAD should be interpreted more cautiously. coronary artery disease; epidemiology; genetics; heme oxygenase 1; HO-1; meta-analysis; polymorphism
Abbreviations: CAD, coronary artery disease; CI, confidence interval; HO-1, heme oxygenase 1; HuGE, Human Genome Epidemiology; OR, odds ratio; SNP, single-nucleotide polymorphism.
Editor’s note: This article also appears on the website of the Human Genome Epidemiology Network (http://www.cdc. gov/genomics/hugenet/default.htm).
(3). The HO-1 gene is located on human chromosome 22 at 22q12 (4). The protein encoded by HO-1 degrades heme to carbon monoxide, bivalent iron cations (Fe2+), and biliverdin, which is then converted to bilirubin by biliverdin reductase (5). As the inducible isoform of heme oxygenase, the HO-1 protein is highly responsive to its substrate, heme, as well as to a broad spectrum of chemical and physical stress agents. Therefore, the induction of HO-1 is considered a biomarker for cell stress (6). Among a panel of described polymorphisms in the HO-1 gene (3, 7, 8), 2 have attracted the most attention: a (GT)n dinucleotide repeat length polymorphism and a common single-nucleotide polymorphism (SNP), T(-413)A (rs2071746). The (GT)n short allele (S,
