Saif-Ali Riyadh, Harun Roslan, Al-Jassabi S, Wan Ngah Wan Zurinah
UKM Medical Molecular Biology Institute, University Kebangsaan, Malaysia.
Acta Biochim Pol. 2011;58(2):179-86. Epub 2011 Jun 2.
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.
本研究旨在调查肝细胞核因子4（HNF4）α单核苷酸多态性（SNP）及单倍型与胰岛素抵抗和代谢综合征参数之间的关联。对160名无糖尿病或代谢综合征的受试者，进行了跨越HNF4α P2启动子（rs4810424、rs1884613和rs1884614）及编码区（rs2144908、rs6031551、rs6031552、rs1885088、rs1028583和rs3818247）的9个SNP的基因分型。HNF4α P2启动子SNP rs4810424、rs1884613和rs1884614与胰岛素抵抗（p = 0.017；0.037；0.024）及体重指数（BMI）（p = 0.03；0.035；0.039）相关。内含子1D SNP rs2144908与高密度脂蛋白胆固醇（HDLc）（p = 0.020）相关，内含子9 SNP rs3818247与收缩压（p = 0.02）和舒张压（p = 0.034）相关。HNF4α常见单倍型CCCGTC与更高的胰岛素抵抗（p = 0.022）、空腹血糖（FBG）（p = 0.035）及更低的HDLc（p = 0.001）相关。总之，具有HNF4α P2变异体和单倍型的受试者已被证明具有更高的胰岛素抵抗，因此患2型糖尿病的风险更高。
