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.
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).


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.
Lim
S C
SC
Department of Medicine, Alexandra Hospital, Singapore. Su_chi_lim@alexhosp.com.sg
Goh
S K
SK
Lai
Y R
YR
Tee
W W
WW
Koh
A
A
Xu
X H
XH
Wu
Y S
YS
Yap
E
E
Subramaniam
T
T
Sum
C F
CF
D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012846:Singapore / Q000453:epidemiology
D019255:NADPH Oxidases; C086986:CYBA protein, human