A Preliminary Study In Relationship Between Smad3and ACE Genes With Diabetic Retinopathy In Type2Diabetes Mellitus

Objective:Many genes have been found to be associated with the pathogenesy of diabetic retinopathy (DR). The study of DR genes has predominantly been undertaken by using the candidate gene approach. TGF-β/Smads signaling pathway and angiotensin-converting enzyme(ACE) play a crucial role in diabetic retinopathy, so we select Smad3gene and the ACE gene as the candidate genes for diabetic retinopathy.In our study, we analyzed three single nucleotide polymorphisms (SNPs) in the intron region of Smad3gene(rs1498506, rs12102171) and ACE gene(rs4353) in412Chinese Han patients with type2diabetes mellitus in order to find susceptible genes of DR.Methods:Four hundred and twelve Chinese Han patients with type2diabetes were recruited from Tianjin Medical University Eye Center in this study. The subjects were classified into three groups:patients with nonproliferative diabetic retinopathy (NPDR group), patients with proliferative diabetic retinopathy (PDR group) and patiens with type2diabetes of a duration of more than10years without diabetic retinopathy and diabetic nephropathy (NDR group). After an overnight fasting,5ml blood was taken from the elbow vein of each subject.2ml blood was used to analyze for biochemisty parameters, included fasting plasma glucose(FPG), glycosylated hemoglobin(HbAlc), total cholesterol(TG), triglyceride(TC), uric acid(UA), blood urea nitrogen(BUN) and serum creatinine(SCR).3ml blood was used to extracted human genomic DNA. Genotyping for the three SNPs of the Smad3gene and ACE gene was carried out by MALDI-TOF-MS (Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry) analysis. SPSS and PLINK were applied to statistical analysis, and a P value of<0.05was considered to be significant. Result:(1)Association analysis for Dichotomous Variable:The rs1498506and rs4353were not associated with DR(P=0.69and P=0.96). The rs12102171was associated with DR (P=0.03). The frequency of rs12102171T allele was higher in DR(39%) than in NDR(23%). The rs1498506and rs4353were also not associates with PDR(P=0.64and P=0.79). The rs12102171was associated with PDR (P=0.03). The frequency of rs12102171T allele was higher in PDR(39%) than in NDR(25%)(2)Association analysis for quantitative traits:The polymorphism of the rs1498506, rs12102171and rs4353were not associated with the biochemisty parameters, including FPG, HbAlc, TC, TG, UA, BUN and SCR(P>0.05)..Conclusion:In Chinese Han patients with type2diabetes mellitus, the rs1498506and rs4353are not associated with DR and PDR, while the rs12102171is associated with DR and PDR. The rs12102171T allele increases the risk of developing diabetic retinopathy.