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  • Title: Association of rs7041 and rs4588 Polymorphisms of the Vitamin D Binding Protein and the rs10741657 Polymorphism of CYP2R1 with Vitamin D Status Among Jordanian Patients.
    Author: Lafi ZM, Irshaid YM, El-Khateeb M, Ajlouni KM, Hyassat D.
    Journal: Genet Test Mol Biomarkers; 2015 Nov; 19(11):629-36. PubMed ID: 26383826.
    Abstract:
    AIM: Previous studies have shown a high prevalence of vitamin D deficiency among Jordanians despite adequate exposure to sunlight, suggesting the presence of other causes for this deficiency. The aim of this study was to identify the relationship between 25-hydroxyvitamin D [25-(OH) VD] status and the nonsynonymous single-nucleotide polymorphisms (SNPs) (rs7041 and rs4588) of the GC gene, which encodes the vitamin D binding protein, and one SNP (rs10741657) near the CYP2R1 gene. METHODS: Blood samples from 381 subjects (74 males and 307 females, 18-60 years of age) were obtained from the "National Center for Diabetes, Endocrinology and Genetics" (Amman, Jordan). The subjects were classified as "apparently healthy" if they did not suffer from chronic diseases and as "unhealthy" if they suffered from certain chronic diseases. Subjects' genotypes for GC; rs7041 and rs4588; CYP2R1; rs10741657 were determined by the polymerase chain reaction-restriction fragment length polymorphism assay method. RESULTS: Apparently, healthy subjects had significantly higher 25-(OH) VD levels than unhealthy patients. In apparently healthy subjects, the rs10743657 genotypes containing the variant allele A (AA, GA) were associated with higher 25-(OH) VD levels than the homozygous wild-type genotype (GG). The genotypes containing the variant allele of rs7041 (TT, TG) and rs4588 (AA, AC) were associated with lower 25-(OH) VD levels than the wild-type genotypes (GG and CC, respectively). Haplotype analysis of rs7041 and rs4588 revealed that the haplotypes GC1S and GC1S/S were associated with 25-(OH) VD sufficiency, whereas haplotypes GC1F/S, GC1F/2, GC1S/2, GC2, and GC2/2 were associated with 25-(OH) VD deficiency. In unhealthy patients, only the homozygous genotype of the variant allele of rs7041 (TT) was associated with higher 25-(OH) VD levels, which is the reverse of what had been observed in apparently healthy subjects. CONCLUSIONS: The rs70141657G/A of CYP2R1 and rs7041T/G and rs4588C/A of vitamin D binding protein genetic polymorphisms were associated with increased risk of vitamin D deficiency among apparently healthy Jordanians.
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