Modification of the effects of estrogen therapy on HDL cholesterol levels by polymorphisms of the HDL-C receptor, SR-BI: the Rancho Bernardo Study
Modification of the effects of estrogen therapy on HDL cholesterol levels by polymorphisms of the HDL-C receptor, SR-BI: the Rancho Bernardo Study
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DOI：
10.1016/j.atherosclerosis.2004.12.013
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发表时间：
2005-06-01
期刊：
影响因子：
5.3
通讯作者：
McCarthy, JJ
中科院分区：
文献类型：
--
作者：
Richard, E;von Muhlen, D;McCarthy, JJ
背景：先前的研究发现，HDL 受体 SR-BI 的多态性与女性血浆 HDL-C 相关，但与男性无关，表明雌激素具有调节作用。我们检查了社区绝经后白人女性中使用非对抗性雌激素是否会改变 SR-BI 基因型与 HDL-C 之间的关联。方法：在 Rancho Bernardo 研究的 689 名女性中评估了 SR-BI 基因内含子 5 和外显子 8 的常见多态性。进行多元线性回归分析以调整混杂因素。结果：HDL-C 水平在总体人群中并没有因基因型而显着差异。然而，雌激素的使用与外显子 8 (p = 0.03)、内含子 5 (p = 0.03) 和内含子 5/外显子 8 双倍型 (p = 0.01) 之间存在显着的相互作用。 SR-BI 基因型仅在雌激素使用者中与 HDL-C 水平相关（p = 0.05），并解释了该组中 HDL-C 差异的 5.3%。与之前的研究一致，Intron5 和 Exon8 基因座杂合的个体具有最低的 HDL-C 水平。在有症状的 CHID 女性中，雌激素的使用与 SR-BI 基因型之间的相互作用变得更强。结论：无对抗的雌激素使用对 HDL-C 的影响可能取决于女性的 SR-BI 基因型。 (c) 2004 Elsevier Ireland Ltd. 保留所有权利。
Background: Previous studies have found polymorphisms of the HDL receptor, SR-BI, to be associated with plasma HDL-C in women, but not men, suggesting a modifying role of estrogen. We examined whether the association between SR-BI genotypes and HDL-C is modified by use of unopposed estrogen in community-dwelling postmenopausal Caucasian women.Methods: Common polymorphisms in Intron5 and Exon8 of the SR-BI gene were evaluated in 689 women from the Rancho Bernardo Study. Multiple linear regression analysis was carried out adjusting for confounders.Results: HDL-C levels did not differ significantly by genotype in the aggregate population. However, significant interaction was found between estrogen use and Exon8 (p = 0.03), Intron5 (p = 0.03) and Intron5/Exon8 diplotypes (p = 0.01). SR-BI genotype was associated with HDL-C levels only among estrogen users (p = 0.05) and explained 5.3% of the variance in HDL-C in this group. Consistent with prior studies, individuals heterozygous at both Intron5 and Exon8 loci had the lowest HDL-C levels. Among women with symptomatic CHID, the interaction between estrogen use and SR-BI genotype became even stronger.Conclusions: The effect that unopposed estrogen use has on HDL-C may depend on a woman's SR-BI genotype. (c) 2004 Elsevier Ireland Ltd. All rights reserved.