Role of Haptoglobin 2-2 genotype on disease progression and mortality among South Indian Chronic Kidney Disease Patients

Abstract Background Haptoglobin (HP), a plasma glycoprotein, binds to free hemoglobin and prevents the loss of iron and kidney damage. Polymorphism in the HP gene affects its enzyme activity, and different genotypes result in varied antioxidant, angiogenic and anti-inflammatory properties. From this background the present work is focused to conduct a prospective case-control study in South Indian population and evaluate whether the HP variants are associated to nondialysis (ND) (CKD stages 1-4) and ESRD (CKD stage 5) patients. Methods and Results Totally 392 CKD patients (nondialysis, ND; n= 170, end-stage renal disease, ESRD; n=222) and 202 healthy individuals were enrolled and collected blood samples were used for determining biochemical parameters and HP genotyping. Gene frequency and biochemical parameters were statistically analyzed for disease association. HP2-2 genotypes were significantly associated with ND and ESRD disease development compared to controls. Higher HP2-2 genotype frequency showed an increased hazard ratio for overall disease progression among ND patients (hazard ratio= 3.86; 95% CI =1.88 to 7.93; P=0.0002). Survival analysis also showed that Non-HP2-2 patients have a statistically significantly decreased risk for mortality compared to patients with the HP2-2 genotype (ESRD patients hazard ratio = 4.05; P= 0.04). Conclusion: The present study confirms that HP2-2 polymorphism was statistically associated with the risk of CKD incidence, progression and mortality of south Indian CKD patients. Concluding our results, the HP2-2 genotype could be an independent predictor of all-cause mortality and disease progression in patients with CKD.