Premium
Relationship between common functional polymorphisms of the p22phox gene (−930A > G and +242C > T) and nephropathy as a result of Type 2 diabetes in a Chinese population
Author(s) -
Lim S. C.,
Goh S. K.,
Lai Y. R.,
Tee W. W.,
Koh A.,
Xu X. H.,
Wu Y. S.,
Yap E.,
Subramaniam T.,
Sum C. F.
Publication year - 2006
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.2006.01916.x
Subject(s) - medicine , diabetic nephropathy , creatinine , endocrinology , genotype , diabetes mellitus , nephropathy , single nucleotide polymorphism , genotyping , type 2 diabetes , population , case control study , gastroenterology , genetics , biology , gene , environmental health
Objective Genetic determinants are important in diabetic nephropathy (DN). Oxidative stress has also emerged as an important pathogenic factor in DN and vascular NADH oxidase is a major source of reactive oxygen species (ROS). Previous small studies reported a strong but contradictory association between functional genetic variation of p22 phox , an important subcomponent of NADH oxidase, and DN. We investigated the association between two common functional single nucleotide polymorphisms (SNPs) (−930 A > G and +242 C > T) and DN in a much larger group of Chinese patients with Type 2 diabetes mellitus (T2DM). Research design and methods Case‐control study of Chinese subjects with long‐standing T2DM (> 10 years). Cases ( n = 306) were subjects with a spot urinary albumin : creatinine ratio (ACR) of > 113 mg/mmol or elevated serum creatinine. Control subjects ( n = 306) had ACR < 3.3 mg/mmol and normal serum creatinine. Genotyping was carried out by standard PCR and restriction fragment length polymorphism analysis. Results Gender distribution, age, duration of diabetes and HbA 1c were similar in cases and control subjects. Distribution of genotypes in the control subjects for both SNPs was consistent with the Hardy–Weinberg equilibrium. Distribution of genotypes did not differ significantly between cases and control subjects for both polymorphisms—+2424C > T: cases CC 84.6%, CT 15.0%, TT 0.4% and control subjects CC 87.6%, CT 11.8%, TT 0.6% ( P = 0.45); −930 A > G: cases AA 40.5%, AG 41.8%, GG 17.7% and control subjects AA 38.2%, AG 49.0%, GG 12.8% ( P = 0.12). Distribution of alleles was also similar—+2424 C > T: cases C 92.2%, T 7.8% and control subjects C 93.5%, T 6.5% ( P = 0.66); −930 A > G cases A 61.4%, G 38.6% and control subjects A 62.7%, G 37.3% ( P = 0.38). We estimated that our study has approximately 80% power to detect a relative risk of 1.65 (for +242 C > T) and 1.35 (for −930 A > G) conferred by the minor allele, respectively. Conclusions In contrast with previous small studies, our data suggest that these SNPs do not confer significantly increased susceptibility to DN secondary to T2DM in Chinese subjects.