title: Association of single nucleotide polymorphisms in the 3'UTR of ERAP1 gene with essential hypertension in the Northeastern Han Chinese.
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±1214.09pg/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.
authors: Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China.
authors: Sibao
authors: S
authors: Yang
authors: Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China.
authors: Xueyan
authors: X
authors: Liu
authors: Department of Gastrointestinal Surgery, China-Japan Union Hospital, Jilin University, Changchun, China.
authors: Yongjian
authors: Y
authors: Gao
authors: Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China.
authors: Mei
authors: M
authors: Ding
authors: Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China.
authors: Bing
authors: B
authors: Li
authors: Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China.
authors: Huan
authors: H
authors: Sun
authors: Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China. Electronic address: hyq2@sina.com.
authors: Yuquan
authors: Y
authors: He
authors: Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China. Electronic address: pyang@jlu.edu.cn.
authors: Ping
authors: P
authors: Yang
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000367:Age Factors; D000368:Aged; D000626:Aminopeptidases / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002681:China; D000075222:Essential Hypertension; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D020413:3' Untranslated Regions; D015778:Minor Histocompatibility Antigens; D000626:Aminopeptidases; C464841:ERAP1 protein, human
keywords: Association study; Endoplasmic reticulum aminopeptidase 1; Essential hypertension; Single nucleotide polymorphism