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首页> 美国卫生研究院文献>Comparative and Functional Genomics >Gene Variation of Endoplasmic Reticulum Aminopeptidases 1 and 2 and Risk of Blood Pressure Progression and Incident Hypertension among 17255 Initially Healthy Women
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Gene Variation of Endoplasmic Reticulum Aminopeptidases 1 and 2 and Risk of Blood Pressure Progression and Incident Hypertension among 17255 Initially Healthy Women

机译：17255名最初健康女性的内质网氨基肽酶1和2的基因变异以及血压升高和突发性高血压的风险

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Recent studies have demonstrated the importance of endoplasmic reticulum aminopeptidase (ERAP) in blood pressure (BP) homeostasis. To date, no large prospective, genetic–epidemiological data are available on genetic variation within ERAP and hypertension risk. The association of 45 genetic variants of ERAP1 and ERAP2 was investigated in 17,255 Caucasian female participants from the Women's Genome Health Study. All subjects were free of hypertension at baseline. During an 18-year follow-up period, 10,216 incident hypertensive cases were identified. Multivariable linear, logistic, and Cox regression analyses were performed to assess the relationship of genotypes with baseline BP levels, BP progression at 48 months, and incident hypertension assuming an additive genetic model. Linear regression analyses showed associations of four tSNPs (ERAP1: rs27524; ERAP2: rs3733904, rs4869315, and rs2549782; all p < 0.05) with baseline systolic BP levels. Three tSNPs (ERAP1: rs27851, rs27429, and rs34736, all p < 0.05) were associated with baseline diastolic BP levels. Multivariable logistic regression analysis showed that ERAP1 rs27772 was associated with BP progression at 48 months (p = 0.0366). Multivariable Cox regression analysis showed an association of three tSNPs (ERAP1: rs469783 and rs10050860; ERAP2: rs2927615; all p < 0.05) with risk of incident hypertension. Analyses of dbGaP for genotype–phenotype association and GTEx Portal for gene expression quantitative trait loci revealed five tSNPs with differential association of BP and nine tSNPs with lower ERAP1 and ERAP2 mRNA expression levels, respectively. The present study suggests that ERAP1 and ERAP2 gene variation may be useful for risk assessment of BP progression and the development of hypertension.
机译：最近的研究表明内质网氨基肽酶（ERAP）在血压（BP）动态平衡中的重要性。迄今为止，尚无关于ERAP内遗传变异和高血压风险的大量前瞻性，遗传流行病学数据。妇女基因组健康研究的17,255名白人女性参与者中研究了ERAP1和ERAP2的45种遗传变异的关联。所有受试者在基线时均无高血压。在为期18年的随访期间，确定了10,216例高血压事件。进行了多变量线性，逻辑和Cox回归分析，以评估基因型与基线BP水平，48个月BP进展以及假设加成遗传模型的高血压的关系。线性回归分析显示四个tSNP（ERAP1：rs27524; ERAP2：rs3733904，rs4869315和rs2549782;所有p <0.05）与基线收缩压水平相关。三个tSNP（ERAP1：rs27851，rs27429和rs34736，所有p <0.05）与基线舒张压BP水平相关。多变量logistic回归分析显示，ERAP1 rs27772与48个月的BP进展相关（p = 0.0366）。多变量Cox回归分析显示三个tSNPs（ERAP1：rs469783和rs10050860; ERAP2：rs2927615;所有p <0.05）与发生高血压的风险相关。 dbGaP的基因型-表型关联分析和GTEx Portal的基因表达定量性状基因座分析显示，分别有5个具有BP差异关联的tSNP和9个具有较低ERAP1和ERAP2 mRNA表达水平的tSNP。本研究表明，ERAP1和ERAP2基因变异可能有助于评估BP进展和高血压的发展。

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