A Functional Common Polymorphism of the ABCB1 Gene Is Associated With Chronic Kidney Disease and Hypertension in Chinese

BACKGROUND Permeability glycoprotein is encoded by the ATP-binding cassette B1 gene (ABCB1) and is an extruder of toxic metabolites in the kidney. A functional common polymorphism (C3435T, rs1045642) in the human ABCB1 gene has been found to be associated with allograft outcome in kidney transplant patients. In this study, we investigated the association of the C3435T polymorphism with renal function and blood pressure (BP) in 2 Chinese populations. METHODS The discovery and replication populations were recruited from a mountainous area (Zhejiang Province) and a newly urbanized suburban area (Shanghai), respectively. We genotyped all subjects using the ABI SNapShot method. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate <60ml/min x 1.73 m(2) or 24-hour urinary albumin excretion >= 30 mg. RESULTS In the discovery population of 1,987 subjects, after adjustment for covariables, TT homozygosity (n = 217) was associated with a higher risk of CKD (n = 369; odds ratio (OR) = 1.73; P = 0.003) and with higher systolic BP (+3.1 mm Hg; P = 0.03) and pulse pressure (+3.4 mm Hg; P = 0.001). These associations were dependent on age (P-int <= 0.05). In subjects aged >= 60 years (n = 374), the corresponding OR or difference was 2.40 for CKD, 15.1 mm Hg for systolic BP, and 12.4 mm Hg for pulse pressure (P < 0.001). In similar adjusted analyses in the replication population of 2,427 elderly (= 60 years) subjects, TT homozygosity was also associated with a higher risk of CKD (OR = 1.39; P = 0.02) and an enhanced association of hypertension with CKD (OR = 1.50; P = 0.04). CONCLUSIONS The ABCB1 C3435T polymorphism might predict CKD, especially in the elderly.