Sedky Nada K, Abdel Rahman Mohamed F, Hassanein Sally I, Gad Mohamed Z
Clinical Biochemistry Unit, Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, New Cairo City, 11835, Egypt.
Biomedical Sciences Program, Zewail City of Science and Technology, Giza, 12566, Egypt.
Curr Pharm Biotechnol. 2018;19(3):265-273. doi: 10.2174/1389201019666180528082737.
Myocardial Infarction (MI) is one of the leading causes of morbidity and mortality in Egypt and worldwide. Vitamin D deficiency has long been linked to incidence of cardiovascular diseases. Several factors were reported to contribute to serum vitamin D level including exposure to sunlight. However, genetic variations in the vitamin D metabolic pathways have also been considered as strong determinants of vitamin D levels. CYP2R1 is the major 25-hydroxylase enzyme that is responsible for the 1st activation step of vitamin D.
to investigate the contribution of polymorphisms in CYP2R1 gene to vitamin D deficiency and incidence of MI in Egyptians.
The study included 323 subjects; 185 MI patients and 138 healthy controls. Serum 25OHD3, 25OHD2 and total 25OHD levels were measured using LC-MS/MS. SNPs rs2060793 and rs1993116 were determined by polymerase chain reaction - restriction fragment length polymorphism (PCRRFLP) which is considered one of the most commonly used techniques in genotyping. SNP rs10766197 was detected using TaqMan allele discrimination assay.
Serum 25OHD3, 25OHD2 and total 25OHD levels were found to be significantly lower in MI patients than controls. The three studied SNPs were associated with significantly different total 25OHD levels and their genotype distributions differed significantly between MI patients and controls where the high risk genotypes were AG/AA for rs2060793, AG/GG for rs1993116 and AG/AA for rs10766197. Additionally, the concurrent presence of high risk genotypes of the three studied SNPs rendered those individuals at extremely higher risk for MI than each individual SNP (OR 14.1, 95% CI (3.1-64.7), p-value = < 0.0001).
Genetic variants of CYP2R1 are key determinants of serum 25OHD levels and are highly associated with MI risk.
心肌梗死（MI）是埃及乃至全球发病和死亡的主要原因之一。长期以来，维生素D缺乏一直与心血管疾病的发病率相关。据报道，包括阳光照射在内的几个因素会影响血清维生素D水平。然而，维生素D代谢途径中的基因变异也被认为是维生素D水平的重要决定因素。CYP2R1是主要的25 - 羟化酶，负责维生素D的第一步激活。
研究CYP2R1基因多态性对埃及人维生素D缺乏和心肌梗死发病率的影响。
该研究纳入323名受试者，其中185名心肌梗死患者和138名健康对照。采用液相色谱 - 串联质谱法（LC - MS/MS）测定血清25OHD3、25OHD2和总25OHD水平。通过聚合酶链反应 - 限制性片段长度多态性（PCRRFLP）检测单核苷酸多态性（SNP）rs2060793和rs1993116，这是基因分型中最常用的技术之一。使用TaqMan等位基因鉴别分析法检测SNP rs10766197。
发现心肌梗死患者的血清25OHD3、25OHD2和总25OHD水平显著低于对照组。所研究的三个SNP与总25OHD水平存在显著差异，其基因型分布在心肌梗死患者和对照组之间也有显著差异，其中rs(2060793)的高风险基因型为AG/AA，rs(1993116)为AG/GG，rs(10766197)为AG/AA。此外，所研究的三个SNP的高风险基因型同时存在使这些个体患心肌梗死的风险比每个单独的SNP个体高得多（比值比14.1，95%置信区间（3.1 - 64.7），p值 = < 0.0001）。
CYP2R1基因变异是血清25OHD水平的关键决定因素，与心肌梗死风险高度相关。
