کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2815863 | 1569844 | 2015 | 6 صفحه PDF | دانلود رایگان |
• Validated the down-regulated expression of ERAP1 in hypertensives with Elisa
• Using methods of direct PCR-sequencing to genotype in the 3′UTR of ERAP1 gene
• Identified two almost complete linkage disequilibrium SNPs significantly associated with essential hypertension
• The association of haplotype C-G with EH was specified in younger population.
Endoplasmic reticulum aminopeptidase 1 (ERAP1) may be involved in blood pressure regulation by inactivation of angiotensin II and generation of bradykinin. Our previous study with cDNA microarray indicated that the expression of ERAP1 is down-regulated in essential hypertension (EH) patients. Since the 3′untranslated region (3′UTR) is known to play an important role in the post-transcriptional regulation by influencing the stability and translation process of mRNA, the present study aims to identify single nucleotide polymorphisms (SNPs) in the 3′UTR of ERAP1 gene in a case–control study among the Northeastern Han Chinese through PCR-sequencing, and analyze the association with EH. Our results further verified the lower expression level of ERAP1 in the peripheral blood cells in patients with EH (917.12 ± 517.57 vs. 1506.59 ± 1214.09 pg/mL, P = 0.011). Four SNPs, 3′UTR-761G>A, 3′UTR-787C>T, 3′UTR-1008A>C and 3′UTR-1055A>G, were identified in the 3′UTR of ERAP1. 3′UTR-1008A>C and 3′UTR-1055A>G were in almost complete linkage disequilibrium. Association analysis showed that the genotypic and allelic frequencies of 3′UTR-1008A>C and 3′UTR-1055A>G were significantly different between EH and the control groups. Logistic regression and haplotypic analysis indicated that alleles of E20-1037C and E20-1084G as well as haplotype of C-G were the risk factors of EH (P < 0.05). Subgroup analysis performed by age suggested that the frequencies of genotype and allele of 3′UTR-1008A>C and 3′UTR-1055A>G as well as the haplotypes C-G and A-A were significantly different between EH and the control in the younger group (< 50), but not in the older group (≥ 50). Younger population with the 3′UTR-1008CC and/or 3′UTR-1055GG genotypes also tended to have higher blood pressure, especially the diastolic blood pressure. In conclusion, the 3′UTR-1008A>C and 3′UTR-1055A>G polymorphisms of ERAP1 gene were associated with EH, especially in the younger population, and the haplotype C-G could be the independent marker of EH.
Journal: Gene - Volume 560, Issue 2, 15 April 2015, Pages 211–216