Genetic variants of CYP2R1 are key regulators of serum vitamin D levels and incidence of myocardial infarction in middle-aged Egyptians

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dc.AffiliationOctober University for modern sciences and Arts (MSA)
dc.contributor.authorSedky N.K.
dc.contributor.authorRahman M.F.A.
dc.contributor.authorHassanein S.I.
dc.contributor.authorGad M.Z.
dc.contributor.otherClinical Biochemistry Unit
dc.contributor.otherBiochemistry Department
dc.contributor.otherFaculty of Pharmacy and Biotechnology
dc.contributor.otherGerman University in Cairo
dc.contributor.otherNew Cairo City
dc.contributor.other11835
dc.contributor.otherEgypt; Zewail City of Science and Technology
dc.contributor.otherGiza
dc.contributor.other12566
dc.contributor.otherEgypt; Biochemistry Department
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherOctober University for Modern Science and Arts (MSA)
dc.contributor.other6th of October City
dc.contributor.otherEgypt
dc.date.accessioned2020-01-09T20:41:05Z
dc.date.available2020-01-09T20:41:05Z
dc.date.issued2018
dc.descriptionScopus
dc.description.abstractBackground: 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.en_US
dc.description.urihttps://www.scimagojr.com/journalsearch.php?q=15581&tip=sid&clean=0
dc.identifier.doihttps://doi.org/10.2174/1389201019666180528082737
dc.identifier.doiPubMed ID 29804528
dc.identifier.issn13892010
dc.identifier.otherhttps://doi.org/10.2174/1389201019666180528082737
dc.identifier.otherPubMed ID 29804528
dc.identifier.urihttps://t.ly/q2RkJ
dc.language.isoEnglishen_US
dc.publisherBentham Science Publishers B.V.en_US
dc.relation.ispartofseriesCurrent Pharmaceutical Biotechnology
dc.relation.ispartofseries19
dc.subject25-hydroxyvitamin Den_US
dc.subjectCYP2R1en_US
dc.subjectEgyptiansen_US
dc.subjectMyocardial infarctionen_US
dc.subjectPolymorphismsen_US
dc.subjectVitamin Den_US
dc.subject25 hydroxyvitamin Den_US
dc.subjectcolecalciferolen_US
dc.subjectgenomic DNAen_US
dc.subjectvitamin Den_US
dc.subjectvitamin D receptoren_US
dc.subjectcholestanetriol 26 monooxygenaseen_US
dc.subjectCYP2R1 protein, humanen_US
dc.subjectcytochrome P450 family 2en_US
dc.subjectvitamin Den_US
dc.subject5' flanking regionen_US
dc.subjectadulten_US
dc.subjectArticleen_US
dc.subjectcardiovascular risken_US
dc.subjectcontrolled studyen_US
dc.subjectCYP2R1 geneen_US
dc.subjectDNA extractionen_US
dc.subjectEgyptianen_US
dc.subjectenzyme linked immunosorbent assayen_US
dc.subjectfemaleen_US
dc.subjectgeneen_US
dc.subjectgene frequencyen_US
dc.subjectgenetic variabilityen_US
dc.subjectgenotypeen_US
dc.subjectheart infarctionen_US
dc.subjectheterozygosityen_US
dc.subjecthigh risk populationen_US
dc.subjecthomozygosityen_US
dc.subjecthumanen_US
dc.subjectintronen_US
dc.subjectliquid chromatography-mass spectrometryen_US
dc.subjectlow risk populationen_US
dc.subjectmajor clinical studyen_US
dc.subjectmaleen_US
dc.subjectmiddle ageden_US
dc.subjectpromoter regionen_US
dc.subjectrestriction fragment length polymorphismen_US
dc.subjectsingle nucleotide polymorphismen_US
dc.subjectvitamin blood levelen_US
dc.subjectblooden_US
dc.subjectEgypten_US
dc.subjectgeneticsen_US
dc.subjectheart infarctionen_US
dc.subjectincidenceen_US
dc.subjectrisken_US
dc.subjectvitamin D deficiencyen_US
dc.subjectCholestanetriol 26-Monooxygenaseen_US
dc.subjectCytochrome P450 Family 2en_US
dc.subjectEgypten_US
dc.subjectFemaleen_US
dc.subjectGenotypeen_US
dc.subjectHumansen_US
dc.subjectIncidenceen_US
dc.subjectMaleen_US
dc.subjectMiddle Ageden_US
dc.subjectMyocardial Infarctionen_US
dc.subjectPolymorphism, Single Nucleotideen_US
dc.subjectRisken_US
dc.subjectVitamin Den_US
dc.subjectVitamin D Deficiencyen_US
dc.titleGenetic variants of CYP2R1 are key regulators of serum vitamin D levels and incidence of myocardial infarction in middle-aged Egyptiansen_US
dc.typeArticleen_US
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