title: Hepatocyte nuclear factor 4 alpha P2 promoter variants associate with insulin resistance.
abstract: This study aimed to investigate the associations of hepatocyte nuclear factor 4 (HNF4) alpha single nucleotide polymorphisms (SNPs) and haplotype with insulin resistance and metabolic syndrome parameters. Nine SNPs spanning the HNF4 alpha P2 promoter (rs4810424, rs1884613 and rs1884614) and coding region (rs2144908, rs6031551, rs6031552, rs1885088, rs1028583 and rs3818247) were genotyped in 160 subjects without diabetes or metabolic syndrome. The HNF4 alpha P2 promoter SNPs rs4810424, rs1884613 and rs1884614 were associated with insulin resistance (p = 0.017; 0.037; 0.024) and body mass index (BMI) (p = 0.03; 0.035; 0.039). The intron 1D SNP rs2144908 was associated with high-density lipoprotein cholesterol (HDLc) (p = 0.020) and the intron 9 SNP rs3818247 showed association with systolic (p = 0.02) and diastolic (p = 0.034) blood pressure. HNF4 alpha common haplotype CCCGTC associated with higher insulin resistance (p = 0.022), fasting blood glucose (FBG) (p = 0.035) and lower HDLc (p = 0.001). In conclusion, subjects with HNF4 alpha P2 variants and haplotypes have been shown to have a higher insulin resistance and are therefore at a higher risk for developing type 2 diabetes mellitus.
authors.affiliation: UKM Medical Molecular Biology Institute, University Kebangsaan, Malaysia.
authors.forename: Riyadh
authors.initials: R
authors.lastname: Saif-Ali
authors.forename: Roslan
authors.initials: R
authors.lastname: Harun
authors.forename: S
authors.initials: S
authors.lastname: Al-Jassabi
authors.forename: Wan Zurinah
authors.initials: WZ
authors.lastname: Wan Ngah
mesh_terms: D000328:Adult; D001786:Blood Glucose; D001794:Blood Pressure; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics*; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D055105:Waist Circumference
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D051557:Hepatocyte Nuclear Factor 4; D008055:Lipids