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基因 MMP-2 多态性改变了镉暴露与高血压风险的关联。

Polymorphisms in gene MMP-2 modify the association of cadmium exposure with hypertension risk.

机构信息

State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, Hubei 430030, China; Department of Clinical Laboratory, Guangdong Women and Children Hospital, Guangzhou, Guangdong, China.

State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, Hubei 430030, China.

出版信息

Environ Int. 2019 Mar;124:441-447. doi: 10.1016/j.envint.2019.01.041. Epub 2019 Jan 23.

Abstract

BACKGROUND

Cadmium exposure has been inconsistently related with hypertension. However, epidemiologic data on the genetic susceptibility to the hypertensive effect of cadmium exposure are limited.

OBJECTIVES

We investigated whether the associations between cadmium exposure and hypertension risk differed by genetic polymorphisms in MMPs genes.

METHODS

The present study of 497 hypertension cases and 497 healthy controls was conducted in a Chinese population. Urinary cadmium levels were measured with inductively coupled plasma-mass spectrometer (ICP-MS). Multivariable logistic regression models were analyzed after controlling major confounders.

RESULTS

Within the multivariable logistic regression models, compared with the lowest tertile, the highest tertile of urinary cadmium had a 1.33-fold (95% CI: 1.01, 1.93) increased risk of hypertension. Carriers of rs243865 T allele and rs243866 A allele in MMP-2 were suggested to have increased risks of hypertension. The associations of urinary cadmium with hypertension risk were modified by rs14070 (P-value for interaction = 0.022) and rs7201 (P-value for interaction = 0.009) in gene MMP-2. Positively significant trends for increasing odds of hypertension with cadmium levels were observed among the wild types of rs14070 and rs7201, respectively.

CONCLUSIONS

Increasing urinary cadmium concentrations were positively associated with hypertension risk in a Chinese population, and the associations were modified by polymorphism of rs14070 and rs7201 in gene MMP-2.

摘要

背景

镉暴露与高血压的关系不一致。然而,关于镉暴露致高血压遗传易感性的流行病学数据有限。

目的

我们研究基质金属蛋白酶(MMPs)基因遗传多态性是否影响镉暴露与高血压风险之间的关联。

方法

本研究纳入了 497 例高血压病例和 497 例健康对照,在中国人群中进行。采用电感耦合等离子体质谱仪(ICP-MS)测定尿镉水平。在控制主要混杂因素后,采用多变量逻辑回归模型进行分析。

结果

在多变量逻辑回归模型中,与尿镉最低三分位相比,最高三分位的尿镉水平使高血压风险增加 1.33 倍(95%可信区间:1.01,1.93)。MMP-2 基因 rs243865 T 等位基因和 rs243866 A 等位基因携带者发生高血压的风险增加。基因 MMP-2 中 rs14070(交互作用 P 值=0.022)和 rs7201(交互作用 P 值=0.009)的多态性改变了尿镉与高血压风险之间的关联。在 rs14070 和 rs7201 的野生型中,随着镉水平的升高,高血压发生的几率呈显著正相关趋势。

结论

在中国人群中,尿镉浓度的升高与高血压风险呈正相关,rs14070 和 rs7201 基因多态性改变了这种关联。

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