The novel and independent association between single-point SNP of NPHP4 gene and renal function in non-diabetic Japanese population: the Takahata study.
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 1.73m(2) (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 1.73m(2); 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.
Konta
Tsuneo
T
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2, Iida-Nishi, Yamagata, Japan. kkonta@med.id.yamagata-u.ac.jp
Takasaki
Satoshi
S
Ichikawa
Kazunobu
K
Emi
Mitsuru
M
Toriyama
Sayumi
S
Satoh
Hitoshi
H
Ikeda
Ami
A
Suzuki
Kazuko
K
Mashima
Yusuke
Y
Shibata
Yoko
Y
Watanabe
Tetsu
T
Kato
Takeo
T
Kawata
Sumio
S
Kubota
Isao
I
D044466:Asian People / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005919:Glomerular Filtration Rate / Q000235:genetics*; D006801:Humans; D007564:Japan; D007668:Kidney / Q000502:physiology*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*
C491578:NPHP4 protein, human; D011506:Proteins