HP 2-2 genotype Predicts Rapid Disease Progression in Nondialysis Patients and Mortality among South Indian ESRD Patients

Abstract Objectives Haptoglobin (HP), a plasma glycoprotein, binds to free hemoglobin and prevents the loss of iron and kidney damage. In a prospective study, we determined whether HP variants (HP 1–1, HP 2 − 1, HP 2–2) are associated with chronic kidney disease (CKD). Design & Methods : From the Southern part of India, 392 CKD patients (nondialysis, ND; n = 170, end stage renal disease, ESRD; n = 222) and 202 healthy individuals were enrolled, and followed up for up to 70 months. The patients' blood samples were used for determining biochemical parameters and HP genotyping. Gene frequency and biochemical parameters were statistically analyzed for disease association. Results Higher HP 2–2 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 HP 2–2 patients have a statistically significantly decreased risk for mortality compared to patients with the HP 2–2 genotype (ESRD patients hazard ratio = 4.05; P = 0.04). Thus, our data confirm that HP 2–2 polymorphism was statistically associated with the risk for all-cause rapid disease progression in CKD patients. Conclusions Concluding our results, HP 2–2 genotype could be an independent predictor of all-cause mortality in patients with CKD.