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肽基甘氨酸-α-酰胺化单加氧酶(PAM)基因 rs13175330A>G 多态性与韩国人群的高血压相关。

The peptidylglycine-α-amidating monooxygenase (PAM) gene rs13175330 A>G polymorphism is associated with hypertension in a Korean population.

机构信息

National Leading Research Laboratory of Clinical Nutrigenetics/Nutrigenomics, Department of Food and Nutrition, College of Human Ecology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.

Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, 03722, South Korea.

出版信息

Hum Genomics. 2017 Nov 21;11(1):29. doi: 10.1186/s40246-017-0125-3.

Abstract

BACKGROUND

Peptidylglycine-α-amidating monooxygenase (PAM) may play a role in the secretion of atrial natriuretic peptide (ANP), which is a hormone involved in the maintenance of blood pressure (BP). The objective of the present study was to determine whether PAM is a novel candidate gene for hypertension (HTN).

RESULTS

A total of 2153 Korean participants with normotension and HTN were included. Genotype data were obtained using the Korean Chip. The rs13175330 polymorphism of the PAM gene was selected from the ten single nucleotide polymorphisms (SNPs) most strongly associated with BP. The presence of the G allele of the PAM rs13175330 A>G SNP was associated with a higher risk of HTN after adjustments for age, sex, BMI, smoking, and drinking [OR 1.607 (95% CI 1.220-2.116), p = 0.001]. The rs13175330 G allele carriers in the HTN group treated without antihypertensive therapy (HTN w/o therapy) had significantly higher systolic and diastolic BP than the AA carriers, whereas the G allele carriers in the HTN group treated with antihypertensive therapy (HTN w/ therapy) showed significantly higher diastolic BP. Furthermore, rs13175330 G allele carriers in the HTN w/o therapy group had significantly increased levels of insulin, insulin resistance, and oxidized low-density lipoprotein (LDL) and significantly decreased LDL-cholesterol levels and LDL particle sizes compared to the AA carriers.

CONCLUSION

These results suggest that the PAM rs13175330 A>G SNP is a novel candidate gene for HTN in the Korean population. Additionally, the PAM rs13175330 G allele might be associated with insulin resistance and LDL atherogenicity in patients with HTN.

摘要

背景

肽基甘氨酸-α-酰胺化单加氧酶(PAM)可能在心房利钠肽(ANP)的分泌中发挥作用,ANP 是一种参与维持血压(BP)的激素。本研究的目的是确定 PAM 是否是高血压(HTN)的新候选基因。

结果

共纳入 2153 名韩国正常血压和 HTN 参与者。使用韩国芯片获得基因型数据。从与 BP 相关性最强的 10 个单核苷酸多态性(SNP)中选择 PAM 基因的 rs13175330 多态性。PAM rs13175330 A>G SNP 的 G 等位基因的存在与调整年龄、性别、BMI、吸烟和饮酒后 HTN 的风险增加相关[OR 1.607(95%CI 1.220-2.116),p=0.001]。未经降压治疗的 HTN 组(HTN w/o 治疗)中 rs13175330 G 等位基因携带者的收缩压和舒张压显著高于 AA 携带者,而经降压治疗的 HTN 组(HTN w/治疗)中 rs13175330 G 等位基因携带者的舒张压显著升高。此外,未经降压治疗的 HTN 组中 rs13175330 G 等位基因携带者的胰岛素、胰岛素抵抗、氧化型低密度脂蛋白(LDL)水平显著升高,而 LDL 胆固醇和 LDL 颗粒大小显著降低。

结论

这些结果表明,PAM rs13175330 A>G SNP 是韩国人群 HTN 的新候选基因。此外,PAM rs13175330 G 等位基因可能与 HTN 患者的胰岛素抵抗和 LDL 致动脉粥样硬化性有关。

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