title: The novel and independent association between single-point SNP of NPHP4 gene and renal function in non-diabetic Japanese population: the Takahata study.
abstract: 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.
authors.affiliation: 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
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Konta
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takasaki
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Ichikawa
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Emi
authors.forename: Sayumi
authors.initials: S
authors.lastname: Toriyama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Satoh
authors.forename: Ami
authors.initials: A
authors.lastname: Ikeda
authors.forename: Kazuko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Mashima
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shibata
authors.forename: Tetsu
authors.initials: T
authors.lastname: Watanabe
authors.forename: Takeo
authors.initials: T
authors.lastname: Kato
authors.forename: Sumio
authors.initials: S
authors.lastname: Kawata
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
mesh_terms: 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*
chemical_list: C491578:NPHP4 protein, human; D011506:Proteins