Association of Certain Vitamin D Metabolizing Enzymes (CYP2R1 and CYP27B1) Genes Polymorphisms with Type 1 Diabetes Mellitus in Jordanian Patients

Abstract

Wiam Y Khalil, Yacoub M Irshaid, Nahla M Khawaja, Mohammed S El-khateeb and Kamel M Ajlouni

Objectives: Type 1 diabetes mellitus (T1DM) is a multifactorial disorder, where environmental and genetic factors may interact and contribute to its pathogenesis. Several T1DM susceptibility genetic loci have been identified using genomewide screens. Among those are loci located in the genes of vitamin D metabolizing enzymes; CYP2R1 (rs10741657 and rs12794714) and CYP27B1 (rs10877012). The aim of this study was to investigate the association of polymorphisms in CYP2R1 (rs10741657 and rs12794714) and CYP27B1 (rs10877012) genes with T1DM.

Methods: The study was performed on 123 T1DM patients and 123 non-diabetic control subjects. It was approved by the “Institutional Review Board” of the National Center for Diabetes, Endocrinology, and Genetics (NCDEG), Amman, Jordan. Polymorphisms in rs10741657, rs12794714 and rs10877012 were studied by genotyping using polymerase chain reaction - restricted fragment length polymorphism (PCR-RFLP) assay method.

Results: A significant association was found between rs12794714 AA genotype and T1DM. The allele was more frequent in T1DM patients (0.524) than in control subjects (0.407) (P-value = 0.0089). No significant association was found between T1DM and rs10741657 and rs10877012 polymorphisms. However, The AA-GG haplotype of CYP2R1 rs12794714 - rs10741657 maintained the association between rs12794714 AA genotype and T1DM. The association between rs12794714 AA genotype and T1DM was enhanced in the presence of CYP27B1 rs10877012 CC genotype (odds ratio increased from 2.71 to 4.27, P = 0.0003).

Conclusion: Our study revealed an association between CYP2R1 rs12794714 AA genotype and T1DM. This association was enhanced in the presence of CYP27B1 rs10877012 CC genotype.

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