| [Purpose] Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus and also a leading cause of visual impairment in diabetic patients. It is well known that DR is associated with metabolic abnormalities induced by long-term hyperglycemia. However, it is unclear of the pathogenesis of DR. A study showed that about28.8%of diabetic patients develop DR in the early stage, but still about22.2%of diabetic patients irrespective of the level of blood glucose do not develop DR. This study revealed that genetic factor may be the initiating agent. Recently, as the development of molecular biology, many studies focused on candidate genes of DR. Peroxisome proliferator-activated receptor-γ(PPARy)gene was one of them. PPARy gene is associated with DR in our meta-analysis, but not obvious in Asian group because of small sample effect. The aim of this study is to investigate the association between the rs1801282,rs3856806,rs12497191of PPARγ gene and DR in the Chinese Han people coming from Shandong province and Beijing by using polymerase chain reaction-1ligase detection reaction(PCR-LDR).[Methods]1.Meta-analysis:An electronic literature search was conducted on PubMed, ISI Web of Knowledge, EMBASE, and the China National Knowledge Internet to do meta-analysis of association between PPARy gene and DR. A dominant model was used to ensure adequate statistical power. Crude odds ratios (ORs) and95%confidence intervals (Cls) were calculated using the fixed effect model. Potential sources of heterogeneity and bias were explored.2.Case-control study:792patients with type2diabetes mellitus(T2DM)were involved, they are all Asian,455of them are DR, DR group was grading according to the Early Treatment Diabetic Retinopathy Study(ETDRS) as two subgroups:Proliferative diabetic retinopathy(PDR) and Non-proliferative diabetic retinopathy (NPDR), other337diabetes patients without DR were enrolled as control in this study. Genomic deoxyribonucleic acid (DNA)was extracted from DR patients and control subjects, then stored in-80℃. The genotypes and alleles of the PPARy gene were analyzed by PCR-LDR. PCR amplification products were verified by electrophoresis on agarose gel. Statistical analyses were performed with SPSS13.0software for Windows. The level of significance adopted was P<0.05. All the measurement data was tested the normality. Normally distributed data was demonstrated by Means±SD and non-normally distributed data by median(inter-quartile range). The genotypes were analyzed by Chi-square test to test whether the genotype distribution followed the Hardy-Weinberg equilibrium. The measurement data was compared by t-test, and the enumeration data was compared by Chi-square test. None-conditional Logistic regression was performed.Genotype and allele frequencies between cases and controls were compared by chi-square analysis. Haplotypes were constructed using observed genotypes by the SHEsis program.[Result]1. Meta-analysis:showed PPARy gene was associated with DR.(OR=0.81;95%Cl:0.68-0.98, p=0.03).The association was obvious in Caucasian group (OR=0.74;95%Cl:0.59-0.94, p=0.01) but not in Asian group (OR=0.77;95%Cl:0.55-1.07, p=0.12).2、 case-control study:(1)rs1801282:The frequency distribution of rs1801282genotypes in DR was that0.2%of homozygous GG,89.1%of homozygous CC, and10.7%of heterozygous CG.The distributions of C allele and G allele were94.4%and5.6%respectively; In healthy control group, the frequency distribution of genotypes was that92.2%of homozygous CC,0of homozygous CC, and 7.8%of heterozygous CG, and the distributions of C allele and G allele were96.1%and3.9%respectively. The result of Hardy-Weinberg equilibrium test was X2=0.122, P=0.458.There was no significant difference between DR and control group in distribution of rs1801282genotypes and alleles (P>0.05).rs3856806:The frequency distribution of rs3856806genotypes in DR was that62.2%of homozygous CC,3.1%of homozygous TT, and34.7%of heterozygous CT The distributions of C allele and T allele were79.6%and20.4%respectively; In healthy control group, the frequency distribution of genotypes was that69.0%of homozygous CC,3.6%of homozygous TT, and27.4%of heterozygous CT, and the distributions of C allele and T allele were82.7%and17.3%respectively. The result of Hardy-Weinberg equilibrium test was X2=0.612, P=0.434.There was no significant difference between DR and control group in distribution of rs3856806genotypes and alleles (P>0.05).rs12497191:The frequency distribution of rs12497191genotypes in DR was that50.4%of homozygous AA,6.7%of homozygous GG, and42.9%of heterozygous AG The distributions of A allele and G allele were71.9%and28.1%respectively; In healthy control group, the frequency distribution of genotypes was that49.4%of homozygous AA,8.2%of homozygous GG, and42.4%of heterozygous AG, and the distributions of A allele and G allele were70.6%and29.4%respectively. The result of Hardy-Weinberg equilibrium test was X2=0.161, P=0.688.There was no significant difference between DR and control group in distribution of rs12497191genotypes and alleles (P>0.05).There were no significant association between the rs1801282、rs3856806、 rs12497191of PPARy gene and DR,although adjusted by blood glucose, blood pressure and duration of DM.The non-conditional Logistic regression analysis showed that the level of HbAlc is a risk factor of DR.Patients with C(rs1801282) allele have higher level of HbAlc and fasting blood-glucose.(2) Haplotype association analysis:There were no haplotype significant associated with DR.(P<0.05) [Conclusions] There were ethnic differences for association between PPARy gene and DR. PPARy gene was associated with DR in Caucasian group; however, the relationship was not significant in Chinese population. The study showed that the level of HbAlc is risk factors of DR. Patients with C allele (rs1801282) have higher level of HbAlc and fasting blood-glucose which elucidated that PPARy gene was associated with the level of HbAlc and FBG in T2DM patients. |
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