Association Study Of Cyclooxy-enase2Gene-765G/C Polymorphism And Type2Diabetic Nephropathy

Background:Diabetes is a disease related to chronic and low-grade inflammation. Cyclooxygenase-2as one of the inflammatory mediators may play a key role in the presence and progression of diabetic nephropathy. This study examines a possible association between Cyclooxygenase-2Gene-765G/C polymorphism with the nephropathy in type2diabetic Chinese. This study aims to investigate the association of Cyclooxygenase-2Gene-765G/C polymorphism and type2diabetic nephropathy.Methods:For the purpose of the study, type2diabetic cases (n=221) and healthy controls (n=171) were selected. Diabetic patients were divided into three groups according to albumin-creatinine-ratio (ACR) levels:the normalbuminuria group (N group, ACR<30mg/g, n=116, duration of disease was8to24years [median12years]); microalbuminuria group (M group,30mg/g≤ACR<300mg/g, n=75, duration of disease was6to24years [median11years]); proteinuria group (P group, ACR≥300mg/g, n=30, duration of disease was6to32years [median14years]). Then type2diabetic subjects were divided into low-GFR group (GFR below60ml/min*m2) and high-GFR group (GFR above60ml/min*m2). Genotyping was tested by Polymerase Chain Reaction Restriction Fragment Length Polymorphism, PCR-RFLP). The frequency of the genotypes and alleles of-765G/C were compared among groups. The clinical data collected and tested from type2diabetic patients were analyzed.Results:1. The genotype distributions in control group and type2diabetic group were in Hardy-Weinberg equilibrium (P>0.05).2. The frequencies of GG、GC、CC genotype in control group and diabetic group were86.55%、13.45%、0%and92.76%、7.24%、0%, the frequencies of G、C allele were93.27%、6.73%and96.38%、3.62%, respectively. The genotype frequencies of two groups were significant different (P<0.05), the frequency of GG genotype of diabetic group was higher than that of control group (92.97%vs86.55%); the allele frequencies of two groups were significant different (P<0.05), the frequency of G allele of diabetic group was higher than that of control group (96.38%vs93.27%).3. No difference of genotype distribution (P=0.836) or allele frequencies (P=0.839) was found between diabetic patients with DN or without DN. No difference of genotype distribution (P=0.861) or allele frequencies (P=0.864) was found between microalbuminuria group and proteinuria group.4. Although the frequency of GG genotype of low-GFR group was higher than that of high-GFR group (96.77%vs91.03%), the difference was not significant (P=0.142); the frequency of G allele of low-GFR group was also higher than that of high-GFR group, but the difference was not significant (P=0.150)5. Logistic regression analysis for risk factors of type2diabetes mellitus:genotype GG/GC (OR4.293,95%CI1.084-16.991, P=0.038)Conclusion:The polymorphism of Cyclooxygenase-2Gene-765G/C in ZheJiang Han population is confirmed. Cyclooxygenase-2Gene-765G/C polymorphism, which may be associated with the type2diabetes mellitus (T2DM), is possibly not associated with the albumin-creatinine-ratio and the decline in renal function in T2DM cases. G allele probably contributes to the T2DM.