Association between heme oxygenase-1 gene promoter polymorphisms and type 2 diabetes in a Chinese population.
The authors aimed to determine whether 2 functional polymorphisms in the heme oxygenase-1 (HO-1) gene promoter are associated with type 2 diabetes mellitus (T2DM). A Chinese case-control study involving 1,103 newly diagnosed T2DM patients, 371 patients with impaired glucose regulation (IGR), and 1,615 controls was performed (December 2004-December 2007). A (GT)(n) microsatellite polymorphism and a single nucleotide polymorphism, T(-413)A, were genotyped, and their functional relevance was evaluated by examining the level of HO-1 protein expression. For the (GT)(n) microsatellite polymorphism, genotypes with the L (GT)(n) allele (>or=25 GT repeats) were associated with increased odds of IGR or T2DM compared with the S/S genotype (<25 GT repeats) (S/L genotype: odds ratio (OR) = 1.35, P = 0.048; L/L genotype: OR = 1.65, P = 0.006). Subsequent haplotype analysis showed that haplotype TL contributed to increased odds of IGR or T2DM compared with haplotype TS (OR = 1.56, P = 0.003). In functional analyses, HO-1 expression level was significantly reduced in persons with IGR and T2DM carrying the L/L (GT)(n) genotype compared with persons with the S/S genotype. Further haplotype combination assay confirmed the functional dominance of the (GT)(n) microsatellite polymorphism over the T(-413)A single nucleotide polymorphism. These results support an association between the HO-1 (GT)(n) microsatellite polymorphism, HO-1 expression levels, and the odds of T2DM.
Song
Fangfang
F
Department of Nutrition and Food Hygiene and MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Li
Xiangyang
X
Zhang
Muxun
M
Yao
Ping
P
Yang
Nianhong
N
Sun
Xiufa
X
Hu
Frank B
FB
Liu
Liegang
L
D000328:Adult; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D016001:Confidence Intervals; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D013223:Statistics as Topic; D011795:Surveys and Questionnaires
D051547:Heme Oxygenase-1