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The novel and independent association between single-point SNP of NPHP4 gene and renal function in non-diabetic Japanese population: the Takahata study

2010; Springer Nature; Volume: 55; Issue: 12 Linguagem: Inglês

10.1038/jhg.2010.113

1435-232X

Tsuneo Konta, Satoshi Takasaki, Kazunobu Ichikawa, Mitsuru Emi, Sayumi Toriyama, Hitoshi Satoh, Ami Ikeda, Kazuko Suzuki, Yusuke Mashima, Yoko Shibata, Tetsu Watanabe, Takeo Kato, Sumio Kawata, Isao Kubota,

Biomedical Research and Pathophysiology

Nephronophthisis (NPHP) 4 gene coding nephrocystin-4 is involved in the development of renal tubules and its congenital mutations cause juvenile end-stage renal disease, NPHP. To investigate the association between single-point single-nucleotide polymorphism (SNP) of NPHP4 gene and renal function, we conducted a cross-sectional study in Japanese population. The subjects of this study were non-diabetic general population consisting of 2604 individuals >40 years in Takahata town, Japan. We genotyped 11 SNPs within NPHP4 gene that displayed frequent minor allele frequencies (>0.1) in Japanese general population. Among 11 SNPs in NPHP4 gene, only rs1287637 that induces amino acid substitution (A (Gln)/T (Leu)), located in the acceptor site of exon 21, showed a significant association with estimated glomerular filtration rate (eGFR; T/T: 81.3±15.6 (n=1886), A/T: 82.0±15.5 (n=652) and A/A: 87.4±21.4 ml min−1 per 1.73m2 (n=66); mean±s.d., P=0.006). This SNP was not in linkage disequilibrium with the surrounding SNPs. The multivariate analysis adjusted with possible confounders showed that the A/T+T/T genotype of rs1287637 was independently associated with reduced renal function (eGFR <90 ml min−1 per 1.73m2; odds ratio (OR) 1.75, 95% confidence interval (CI) 1.05–2.94, P=0.033). These results indicate the novel and independent association between single-point SNP rs1287637 in NPHP4 gene and renal function in non-diabetic Japanese population.