Department of Biochemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Egypt.
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA.
Steroids. 2021 May;169:108825. doi: 10.1016/j.steroids.2021.108825. Epub 2021 Mar 17.
Vitamin D deficiency has been linked to cardiovascular pathologies including acute coronary syndrome (ACS). Polymorphisms in vitamin D associated genes have been confounding to vitamin D serum levels and pathological predispositions. 7-hydrocholesterol is a common precursor in cholesterol and vitamin D synthesis. DHCR7/NADSYN1 genetic locus expresses 7-hydrocholesterol reductase (DHCR7), an enzyme that recruits 7-hydrocholesterol in cholesterol biosynthesis, and NAD synthetase 1 (NADSYN1), which participates in the hydroxylation of 25 hydroxyvitamin D.
This study aims to correlate two polymorphisms in the DHCR7/NADSYN1 genetic locus with levels of circulatory vitamin D and the presentation of ACS in an Egyptian population.
In a case control study, 189 ACS patients and 106 healthy control subjects were genotyped for SNPs rs11606033 of the DHCR7 gene and rs2276360 of the NADSYN1 gene using the amplification-refractory mutation system (ARMS). The levels of 25(OH)D2 and 25(OH)D3 were measured using an in-house developed and validated ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) based protocol.
ACS patients have significantly lower levels of circulating vitamin D in comparison to healthy controls. Allele A of the DHCR7 polymorphism was found to correlate with serum vitamin D deficiency and incidence of ACS classes: NSTEMI, STEMI and unstable angina, when compared to allele G. On the other hand, the NADSYN1 polymorphism rs2276360 correlated with serum 25(OH)D3 deficiency. Yet, no significant correlation was found with incidences of ACS.
We conclude that rs11606033, which is an intronic SNP between exon 4 and exon 5 of the DHCR7 gene, influences vitamin D serum abundance and more importantly ACS incidence.
维生素 D 缺乏与包括急性冠状动脉综合征 (ACS) 在内的心血管病理有关。维生素 D 相关基因的多态性一直干扰着维生素 D 血清水平和病理易感性。7-羟胆固醇是胆固醇和维生素 D 合成的常见前体。DHCR7/NADSYN1 基因座表达 7-羟胆固醇还原酶 (DHCR7)，该酶在胆固醇生物合成中招募 7-羟胆固醇，以及 NAD 合成酶 1 (NADSYN1)，其参与 25 羟维生素 D 的羟化。
本研究旨在关联 DHCR7/NADSYN1 基因座中的两个多态性与埃及人群中循环维生素 D 水平和 ACS 的表现。
在病例对照研究中，使用扩增不可避免突变系统 (ARMS) 对 189 例 ACS 患者和 106 例健康对照者的 DHCR7 基因 rs11606033 和 NADSYN1 基因 rs2276360 进行了基因分型。使用内部开发和验证的超高效液相色谱串联质谱 (UPLC-MS/MS) 基于方案测量 25(OH)D2 和 25(OH)D3 的水平。
与健康对照组相比，ACS 患者的循环维生素 D 水平显著降低。与等位基因 G 相比，DHCR7 多态性的等位基因 A 被发现与血清维生素 D 缺乏和 NSTEMI、STEMI 和不稳定型心绞痛的 ACS 类相关。另一方面，NADSYN1 多态性 rs2276360 与血清 25(OH)D3 缺乏相关。然而，与 ACS 的发生率没有发现显著相关性。
我们得出结论，DHCR7 基因外显子 4 和外显子 5 之间的内含子 SNP rs11606033 影响维生素 D 血清丰度，更重要的是影响 ACS 的发生率。
