Volume 48, Number 7, 1335-1338, DOI: 10.1007/s00125-005-1785-4

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European Association for the Study of Diabetes

Polymorphism of the solute carrier family 12 (sodium/chloride transporters) member 3, SLC12A3, gene at exon 23 (+78G/A: Arg913Gln) is associated with elevation of urinary albumin excretion in Japanese patients with type 2 diabetes: a 10-year longitudinal study

K. Nishiyama, Y. Tanaka, K. Nakajima, A. Mokubo, Y. Atsumi, K. Matsuoka, H. Watada, T. Hirose, T. Nomiyama and S. Maeda, et al.

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Abstract

Aims/hypothesis  

We have shown previously that the SLC12A3 +78G/A polymorphism in exon 23 (Arg913Gln) was a new candidate for conferring susceptibility to diabetic nephropathy. The aim of this study was to confirm the effect of this polymorphism on the elevation of urinary albumin excretion in type 2 diabetic patients.

Methods  

We retrospectively studied 264 Japanese patients with type 2 diabetes over a ten-year period. The subjects were classified into two groups: (1) persistent normoalbuminuria or microalbuminuria, or improvement from microalbuminuria to normoalbuminuria (group N); and (2) progression from normoalbuminuria to microalbuminuria or overt proteinuria, or progression from microalbuminuria to overt proteinuria (group P). They were assessed for association with the +78G/A polymorphism.

Results  

The frequency of the +78A allele was significantly higher in group N than in group P (10% vs 1%, p=0.021). By logistic regression analysis and discriminant analysis, the substituted allele was shown to be an independent factor correlating negatively to the elevation of albumin excretion (p=0.043 and 0.022, respectively).

Conclusions/interpretation  

The SLC12A3 +78A(+) genotype may have a protective effect against the development and/or progression of diabetic nephropathy in Japanese type 2 diabetic patients.

Keywords  Genotype - Japanese - Longitudinal study - Macroalbuminuria - Microalbuminuria - Nephropathy - Polymorphism - SLC12A3 - Solute carrier family 12 - Type 2 diabetes

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