Common Genetic Variation in Nephrin (NPHS1) and its Associations with Renal and Type 2 Diabetes Mellitus-Related Traits

Abstract

Nephrin encoded by NPHS1 is mutated in congenital nephrotic syndrome. NPHS1 variants found in the healthy population may influence slit diaphragm permeability in acquired diabetic nephropathy. Extra-renal nephrin in the human pancreas has a role in insulin secretion and possibly T2DM. Therefore, this study investigated the associations of NPHS1 SNPs with renal and T2DM-related traits. Six SNPs were genotyped in all SDCS and NHS98 subjects. Individual SNPs and haplotypes were not associated with albuminuria and eGFR in T2DM patients. However, NPHS1 haplotypes were associated with slopes of eGFR over age in T2DM. Referencing against the common T/G/A/T/T/A haplotype, carriers of T/G/G/C/T/A and C/A/A/T/T/A had higher eGFR values among younger patients but had lower eGFR values as age increased (P=2.9x10-8; P<0.0001). In contrast, T/G/A/T/T/G carriers had a markedly lower eGFR value with increasing age (P=1.9x10-5). NPHS1 was not associated with T2DM and T2DM-related traits in Chinese, Malays and Asian Indians.