Genetic variation and association analyses of NEDD4 gene in Kazak Chinese patients with hypertension

摘要

To analyze the association between the genetic variations of neural precursor cell expressed developmentally down-regulated 4 gene (NEDD4) and hypertension in Kazakh Chinese. The sequences of NEDD4 gene exons were sequenced in 96 Kazakh Chinese with hypertension to identify representative variations. A case-control study was conducted by genotyping the representative variations in 287 Kazakh hypertensives and 411 normotensives. Replication population was 343 Uygur hypertensives and 724 normotensives. All subjects were selected from population-based cross-sectional studies of metabolic disease. Thirteen novel and 15 known single nucleotide polymorphism (SNPs) or mutations, including 6 missense mutations, were identified. Of the four representative SNPs geno-typed, only rs2303580 was association with hypertension in Kazakh (additive P/Pc=0.020/0.160) without Bonferroni's correction. The result was replicated in Uygur (additive/dominant P=0.089/0.028, Pc=0.174/0.056). By adjusting for age and BMI, the observed association would no longer be statistically significant in Kazakh (additive OR (95%CI) 1.035(0.802-1.336), but remained statistically significant in Uygur ( additive/dominant ORs (95%CI) 1.323 (1.069-1.637), 1.521(1.146-2.020)). The rs2303580 genotypes were not association with blood pressure levels in Kazakh. Although by multiple linear regression analysis and by applying Bonferroni's correction, the genotypes were significant association with diastolic blood pressure levels (AA>AG>GG) in Uygur normotensive controls (P/Pc=0.003/0.018), the direction of difference was not in accordance with the association between the qualitative hypertension phenotype and the genotype shown (G risk allele). Our data indicates that the association between the NEDD4 genetic polymorphisms and hypertension phenotype should be replicated in further studies using larger and racially diverse populations.