Sedky N.K.Rahman M.F.A.Hassanein S.I.Gad M.Z.Clinical Biochemistry UnitBiochemistry DepartmentFaculty of Pharmacy and BiotechnologyGerman University in CairoNew Cairo City11835Egypt; Zewail City of Science and TechnologyGiza12566Egypt; Biochemistry DepartmentFaculty of PharmacyOctober University for Modern Science and Arts (MSA)6th of October CityEgypt2020-01-092020-01-09201813892010https://doi.org/10.2174/1389201019666180528082737PubMed ID 29804528https://t.ly/q2RkJScopusBackground: 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. Objective: to investigate the contribution of polymorphisms in CYP2R1 gene to vitamin D deficiency and incidence of MI in Egyptians. Methods: 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 (PCR-RFLP) which is considered one of the most commonly used techniques in genotyping. SNP rs10766197 was detected using TaqMan allele discrimination assay. Results: 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). Conclusions: Genetic variants of CYP2R1 are key determinants of serum 25OHD levels and are highly associated with MI risk. � 2018 Bentham Science Publishers.English25-hydroxyvitamin DCYP2R1EgyptiansMyocardial infarctionPolymorphismsVitamin D25 hydroxyvitamin Dcolecalciferolgenomic DNAvitamin Dvitamin D receptorcholestanetriol 26 monooxygenaseCYP2R1 protein, humancytochrome P450 family 2vitamin D5' flanking regionadultArticlecardiovascular riskcontrolled studyCYP2R1 geneDNA extractionEgyptianenzyme linked immunosorbent assayfemalegenegene frequencygenetic variabilitygenotypeheart infarctionheterozygosityhigh risk populationhomozygosityhumanintronliquid chromatography-mass spectrometrylow risk populationmajor clinical studymalemiddle agedpromoter regionrestriction fragment length polymorphismsingle nucleotide polymorphismvitamin blood levelbloodEgyptgeneticsheart infarctionincidenceriskvitamin D deficiencyCholestanetriol 26-MonooxygenaseCytochrome P450 Family 2EgyptFemaleGenotypeHumansIncidenceMaleMiddle AgedMyocardial InfarctionPolymorphism, Single NucleotideRiskVitamin DVitamin D DeficiencyArticlehttps://doi.org/10.2174/1389201019666180528082737PubMed ID 29804528