title: Association of four insulin resistance genes with type 2 diabetes mellitus and hypertension in the Chinese Han population.
abstract: Insulin resistance plays an important role in the development of type 2 diabetes mellitus (T2DM) and hypertension. The purpose of the present study was to evaluate the association between four insulin resistance genes (ADIPOQ, LEPR, RETN, and TRIB3) and both T2DM and hypertension. A total of 768 Han Chinese subjects were recruited into this study, including 188 cases who had T2DM alone, 223 cases who had hypertension alone, 181 cases with both T2DM and hypertension, and 176 control subjects with neither T2DM nor hypertension. Twenty-three tag SNPs in four insulin resistance genes were genotyped and analyzed for association with T2DM and hypertension. One intron SNP (rs13306519) in LEPR and one 3'UTR SNP (rs1063537) in ADIPOQ demonstrated a significant association with T2DM (P = 0.024 and 0.014 respectively). Another intron SNP (rs12037879) in LEPR and a promoter region SNP (rs266729) in ADIPOQ were significantly associated with hypertension (P = 0.041 and 0.042, respectively). These associations survived the permutation test (P = 0.023, 0.018, 0.026, and 0.035, respectively). These associations were still found to be significant in the additive model after adjusting for potential confounding factors including age, sex, BMI, HDL, LDL, total cholesterol, and triglyceride levels (P = 0.024, 0.016, 0.04, and 0.043, respectively). No other gene variants were found to be significantly associated with T2DM or hypertension (P > 0.05). None of the studied gene variants were found to be significantly associated with T2DM+ hypertension (P > 0.05). A significant interaction was observed between two SNPs rs13306519 in LEPR and rs266729 in ADIPOQ for T2DM (P_int = 0.012, OR_int = 2.67) and hypertension (P_int = 0.0041, OR_int = 2.23). These findings suggest that variants in ADIPOQ and LEPR are risk factors for T2DM and hypertension in the Chinese population and that variants in RETN and TRIB3 are not major risk factors for these diseases.
authors.affiliation: Hospital Management Office & School of Public Health, Jilin University, Changchun, China, jiangb@jlu.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.forename: Ya
authors.initials: Y
authors.lastname: Liu
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Li
mesh_terms: D052242:Adiponectin / Q000235:genetics*; D000328:Adult; D044466:Asian People; D018797:Cell Cycle Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000473:pathology; D007328:Insulin / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D054411:Receptors, Leptin / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D052243:Resistin / Q000235:genetics*
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D018797:Cell Cycle Proteins; D007328:Insulin; C515448:LEPR protein, human; C499624:RETN protein, human; D054411:Receptors, Leptin; D012097:Repressor Proteins; D052243:Resistin; C474831:TRIB3 protein, human; D017346:Protein Serine-Threonine Kinases