TNF-α (-308 G→A) Polymorphism and the Risk of Progression to End Stage Renal Disease in Nephropathy Patients

Aims: This hospital based case-control study sought to analyze the association between the promoter region polymorphism in TNF-α and the risks of developing end stage renal disease in nephropathy subjects.

Methodology: 222 documented cases of end stage renal disease (Males=148, Females=74) subjects and 250 healthy controls (Males=130, Females=120) were included in the study. Among 222 cases, 126 subjects had hypertensive nephropathy and 96 had glomerulonephritis as contributing factors of ESRD. Clinical and demographic data was collected from each case. TNF-α (-308 G→A) promoter polymorphism was analyzed by selective amplification by polymerase chain reaction and subsequent digestion by NcoI restriction enzyme. Genotypic and allelic frequencies were compared to controls using Chi-square and Odds ratio analysis. Clinical parameters were compared across genotypes using logistic regression. The probability values were adjusted for age and gender.

Results: Mean age of cases and controls was 47.78 and 46.83 years respectively. Genotypes for TNF-α -308 followed Hardy Weinberg equilibrium (P=0.17). The frequency of homozygous wild, heterozygous and homozygous rare genotypes in cases and controls was 62.6%, 31.08%, 6.3% and 74%, 23.6%, 2.4% respectively (P=0.019). Comparison of genotypes between cases and controls showed an association of AA genotype with ESRD (P=0.02, OR=3.1, 95%CI=1.1-6.2). The AA genotype was significantly associated with lower age in cases (P=0.008) as well as lower serum protein (P=0.03) and calcium levels (P=0.01).

Conclusion: TNF-α (-308 G→A) promoter polymorphism is associated with nephropathy and the carriers of AA genotype exhibit an increased risk towards rapid progression of ESRD.