1. Association of single nucleotide polymorphisms in the 3′UTR of ERAP1 gene with essential hypertension in the Northeastern Han Chinese.
- Author
-
Yang, Sibao, Liu, Xueyan, Gao, Yongjian, Ding, Mei, Li, Bing, Sun, Huan, He, Yuquan, and Yang, Ping
- Subjects
- *
SINGLE nucleotide polymorphisms , *HYPERTENSION , *ENDOPLASMIC reticulum , *AMINOPEPTIDASE genetics , *BRADYKININ , *ANTISENSE DNA , *BLOOD pressure measurement - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF