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 440 years in Takahata town, Japan. We genotyped 11 SNPs within NPHP4 gene that displayed frequent minor allele frequencies (40.1) 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 (n¼1886), A/T: 82.0 ± 15.5 (n¼652) and A/A: 87.4 ± 21.4 ml min À1 per 1.73m 2 (n¼66); mean ± s.d., P¼0.006). 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 o90 ml min À1 per 1.73m 2 ; odds ratio (OR) 1.75, 95% confidence interval (CI) 1.05-2.94, P¼0.033). These results indicate the novel and independent association between single-point SNP rs1287637 in NPHP4 gene and renal function in non-diabetic Japanese population.

Combined effect of mitochondrial DNA 5178 C/A polymorphism and alcohol consumption on estimated glomerular filtration rate in male Japanese health check-up examinees: a cross-sectional study

“…In addition, promoter polymorphism of the endotoxin receptor [19], single nucleotide polymorphism rs1287637 in the nephronophthisis 4 gene is associated with mildly decreased eGFR (<90 ml/min/1.73 m 2 ) [20]. Therefore, these molecular epidemiological studies, as well as our results, indicate gene-gene or gene-gene-environment interactions on renal function.…”

“…Renal function was evaluated by estimated glomerular filtration rate (eGFR), which was calculated using a three-variable Japanese equation: eGFR = 194 × creatinine − 1.094  × age − 0.287 [27]. Similarly to other genetic epidemiological studies [19,20], based on K/DOQI CKD classification [3], reduced eGFR was considered to be <90 ml/min/1.73 m 2 . Body mass index (BMI) was defined as the ratio of subject weight (kg) to the square of subject height (m).…”

Discover hidden splicing variations by mapping personal transcriptomes to personal genomes

“…Indeed, we successfully captured a known personal specific 3′ splice site of intron 20 in NPHP4 associated with SNP rs1287637 ( T > A on the RNA sense strand which created an ‘AG’ 3′ splice site). NPHP4 is involved in renal function and its mutations are known to cause juvenile end stage renal disease ( 43 ). The personal splice junction is supported by 5 distinct reads, though it is unlikely to be identified through traditional reference genome based RNA-seq mapping because the supporting reads are unmappable to hg19 due to the lack of canonical splice site dinucleotides in the reference genome.…”

Association of the Aspartate Aminotransferase to Alanine Aminotransferase Ratio with BNP Level and Cardiovascular Mortality in the General Population: The Yamagata Study 10-Year Follow-Up

“…Estimated glomerular filtration rate (eGFR) was calculated by the modification of diet in renal disease (MDRD) equation with the Japanese coefficient [17, 18]. …”