Association of single nucleotide polymorphisms in the 3'UTR of ERAP1 gene with essential hypertension in the Northeastern Han Chinese

Sibao Yang; Xueyan Liu; Yongjian Gao; Mei Ding; Bing Li; Huan Sun; Yuquan He; Ping Yang

doi:10.1016/j.gene.2015.02.005

Association of single nucleotide polymorphisms in the 3'UTR of ERAP1 gene with essential hypertension in the Northeastern Han Chinese

Gene. 2015 Apr 15;560(2):211-6. doi: 10.1016/j.gene.2015.02.005. Epub 2015 Feb 7.

Authors

Sibao Yang¹, Xueyan Liu¹, Yongjian Gao², Mei Ding¹, Bing Li¹, Huan Sun¹, Yuquan He³, Ping Yang⁴

Affiliations

¹ Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China.
² Department of Gastrointestinal Surgery, China-Japan Union Hospital, Jilin University, Changchun, China.
³ Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China. Electronic address: hyq2@sina.com.
⁴ Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China. Electronic address: pyang@jlu.edu.cn.

PMID: 25665737
DOI: 10.1016/j.gene.2015.02.005

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.

Keywords: Association study; Endoplasmic reticulum aminopeptidase 1; Essential hypertension; Single nucleotide polymorphism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions
Adult
Age Factors
Aged
Aminopeptidases / genetics*
Base Sequence
Case-Control Studies
China
Essential Hypertension
Female
Gene Frequency
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Hypertension / genetics*
Linkage Disequilibrium
Male
Middle Aged
Minor Histocompatibility Antigens
Polymorphism, Single Nucleotide*
Sequence Analysis, DNA

Substances

3' Untranslated Regions
Minor Histocompatibility Antigens
Aminopeptidases
ERAP1 protein, human