Arg913Gln Of SLC12A3 Gene Promotes Development And Progression Of End-stage Renal Disease In Chinese Type 2 Diabetes Mellitus

OBJECTIVE: SLC12A3 is a sodium-chloride cotransporter,which regulates re-absorption of sodium ions and chloride ions in the renal distal convoluted tubules,associates with regulation of blood pressure and is the target of thiazide diuretics.Whether Arg913 Gln variation(rs11643718,G/A)of SLC12A3 contributes to type 2 diabetic kidney disease(DKD)remains controversial.We undertook a case-control study to evaluate the association of the SLC12A3-Arg913 Gln variation with the risk of ESRD in Chinese type 2 diabetes(T2DM)patients undergoing hemodialysis and analyzed the genotype-phenotype interaction.RESEARCH DESIGN AND METHODS: Unrelated Chinese T2 DM patients(n=372)with diabetic retinopathy were classified into the non-diabetic nephropathy control group(non-DKD group,n=151,duration of diabetes >15 years,no signs of renal involvement)and the ESRD group due to T2DM(DKD-ESRD group,n=221;ESRD patients who are receiving hemodialysis).PCR-direct sequencing was used to genotype SLC12A3-Arg913 Gln variation for all 372 subjects.RESULTS: 1)The frequenciey of the GA+AA genotype in DKD-ESRD subjects was significantly higher than that of non-DKDgroup(23.1% vs.9.9%;adjusted OR 2.2(95% CI,1.3-4.5;P=0.019);2)In the non-DKD group,GA+AA carriers had a significantly higher urinary albumin excretion rate(UAER)and diastolic blood pressure(DBP)compared with GG carriers(both P<0.05).CONCLUSIONS: The SLC12A3-Arg913 Gln variation may be associated with elevated blood pressure and UAER,and therefore may predict the development and progression of DKD-ESRD in Chinese T2 DM patients undergoing hemodialysis.