Role of haptoglobin 2-2 genotype on disease progression and mortality among South Indian chronic kidney disease patients.

Background: Haptoglobin (HP), a plasma glycoprotein, binds to free hemoglobin and prevents the loss of iron and kidney damage. The variations of HP gene affect its enzyme activity, resulting in varied antioxidant, angiogenic and anti-inflammatory properties. HP 2-2 genotype showed 3.84 fold increased risk for the development of CKD in Taiwan population. With this background, the present work focused to conduct a prospective case-control study in South Indian population to evaluate whether the HP variants are associated to nondialysis (ND) (CKD stages 1-4) and ESRD (CKD stage 5) conditions.

Methods And Results: Totally 392 CKD patients (nondialysis, ND; n = 170, end-stage renal disease, ESRD; n = 222) and 202 healthy individuals were enrolled. The blood samples collected from the patients were used to determine biochemical parameters and HP genotyping. Gene frequency and biochemical parameters were statistically analyzed for disease association. Results showed that HP 2-2 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 is statistically associated with the risk of CKD incidence, progression, and mortality among South Indians. Concluding our results, the HP2-2 genotype could be an independent predictor of all-cause mortality and disease progression in patients with CKD.