Genetic variation distribution of neural precursor cell expressed developmentally down-regulated 4 gene and its association with metabolic syndrome in Kazak ethnic group

Objective To investigate the gene polymorphism of neural precursor cell expressed developmentally down-regulated 4 (NEDD4) and its association with metabolic syndrome (MS) in Kazak ethnic group. Methods A total of 923 subjects (741 controls and 182 MS patients) from Kasak ethnic group were included in this case-control study based on epidemiologic survey. Genetic variations in NEDD4 were studied with gene sequencing, and Taqman- PCR was used to identify the genotypes of typical genetic variations. Results Twenty-seven genetic variations, including 6 missense mutations, were identified. The frequency distributions of five common single nucleotide polymorphisms (SNPs) did not differ between MS and controls (P＞0.05). After stratification by age, the SNP rs11550869 was associated with MS in Kazak patients aged ≥40 years (P=0.024 for both genotypee and dominant models). After adjusted for age and gender, the odd ratio was 1.604 (95％CI: 1.061-2.424, P=0.025) and 1.681 (95％CI: 1.073-2.633, P=0.023), respectively. Although the three genotypes of SNP rs11550869 polymorphism did not differ in frequency distribution or phenotypes (P＞0.05), the values or levels of waist circumference, body mass index, fasting blood glucose, 2-hour postprandial glucose and HOMA index tended to be increasing from GG to GC and to CC. Moreover, haplotype 5 (A-A-T-A-C, containing the C allele of rs11550869) appeared to be more common in MS subjects as comparea to controls (Permutation test, P=0.059). Conclusion The SNP rs11550869 of NEDD4 gene may be associated with MS in Kazak population aged 40 years or older, although this finding warrants validation in further studies. Key words: Genetic research; Metabolic syndrome; Kazak; Neural precursor cell expressed developmentally down-regulated 4; Genetic association study