Association Of The P22phox Component Of NAD(P)H Oxidase With Susceptibility To Diabetic Nephropathy In Patients With Type 2 Diabetes

Background and Object Diabetetic nephropathy(DN) is one of the most serious complications of diabetes mellitus and the leading cause of end stage renal disease. There is an obvious genetic susceptibility of DN.A considerale body of clinical and experimental evidence now exists suggesting the involvement of free radical- mediated oxidative process in the pathogenesis of diabetetic complications. The reduced form of nicotinamide-adenine dinucleotide phosphate oxidase(NAD(P)H oxidase) is the main source of oxygen free radicals in the vascular cells. P22phox is a subunit of NAD(P)H oxidase and have a close relationship to it's activity.Recent investigations have indicated that genetic variations in p22phox play a role in the pathogenesis of macroangiopathy and microangiopathy.This study aims to investigate the relation between p22phox 242C/T gene polymorphism in exon 4 and the development of nephropathy in type 2 diabetic patients.Methods P22phox gene C242T variant was determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) in 68 healthy controls and 132 patients with type 2 diabetes including 75 with diabetic nephropathy(DN+ group) and 62 without diabetic nephropathy(DN- group);56 with diabetic retinopathy (DR+ group) and 81 without diabetic retinopathy(DR- group).P22phox genotype and allele frequencies were compared among groups.And we had a comparison of clinical characteristics of different p22phox genotype groups in type 2 diabetic patients.Result (1)We found no TT genotype in all subjects;(2)The frequencies of the CT genotype and T allel in control group and DN- group were significantly higher than those in DN+ group(all P<0.05).Compared with DN- group,the odds ratio for T allele of DN+ group was 0.261(95%CI 0.069-0.985);(3) The frequencies of the CT genotype and T allel in control group and DR- group were higher than those in DR+ group.But the differences were not significant(all P>0.05);(4)The genotype frequency for CT and theallel frequency for T were not significantly different among DN- group^ DR- group and control group(all P>0.05);(5) The differences of clinical characteristics between two genotype groups were not significant(all P>0.05).Conclusion The 242C/T polymorphism of the p22phox gene may be a novel genetic marker that has a protective effect on diabetic nephropathy risk in type 2 diabetic patients in Hubei Chinese.The frequencies of the CT genotype and T allel in the DR+ group were lower than those of DR- group,but the differences were not significant.