Date of Award

4-2019

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Dr. Youssef A Abouzaid

Second Advisor

Dr. Bassam Ali

Third Advisor

Dr. Sameh S.M. Soliman

Abstract

Vitamin D normal levels are vital to many biological processes including its classical role in calcium and phosphate homeostasis, and regulation of immune and non-immune cells. Vitamin D mediates its actions via the vitamin D receptor (VDR) which is expressed in most tissues of the body including the airway smooth muscle. Asthma is a syndrome of chronic inflammatory airway disease. There is a genetic and immunological link between vitamin D and asthma. In this study, we aim to investigate whether asthma and its severity were associated with single nucleotide polymorphisms (SNPs) in vitamin D metabolic genes as well as vitamin D levels in asthmatic adult Emiratis. We conducted a case-control study that included 132 adult asthmatic patients and 164 non-asthmatic controls of both sexes. Four SNPs in VDR gene (rs731236, rs7975232, rs1544410, and rs2228570), one SNP in vitamin D 25- hydroxylase gene (CYP2R1; rs12794714) and two SNPs in vitamin D binding protein gene (GC; rs4588 and rs7041) were genotyped using TaqMan Real-Time PCR genotyping techniques, whereas vitamin D levels were measured using electrochemiluminescence binding assay.

Results revealed a statistically significant association between VDR; rs7975232 polymorphism and asthma severity in the homozygous recessive model (OR = 2.7, 95% CI = 1.12-6.56, P = 0.03) and in allele model (OR = 1.74, 95% CI = 1.04-2.9, P = 0.032). The ACG haplotype for VDR; rs731236, VDR; rs7975232, and VDR; rs1544410 was significantly linked with asthma severity (P = 0.045). There was no association between any of the SNPs and mild asthma. There was no statistically significant difference in vitamin D levels between asthmatic patients and controls, and 56.6% of asthmatic patients with normal vitamin D levels were taking vitamin D supplementation. In conclusion, VDR; rs7975232 is significantly associated with asthma severity, and the CC genotype increases the risk of severe asthma by 2.7-fold. Moreover, the ACG haplotype of three SNPs in the VDR gene showed a significant association with asthma severity. VDR; rs7975232 polymorphism may be considered as a biomarker for asthma severity and possibly play a role in the management of asthma in adult Emirati patients.

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