Alharazy Shatha, Naseer Muhammad Imran, Alissa Eman, Robertson M Denise, Lanham-New Susan, Alqahtani Mohammad H, Chaudhary Adeel G
Department of Physiology, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Saudi Arabia.
Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
Saudi J Biol Sci. 2021 Aug;28(8):4626-4632. doi: 10.1016/j.sjbs.2021.04.071. Epub 2021 May 4.
Group-specific component () and cytochrome P450 Family 2 Subfamily R Member 1 () genes are one of the vital genes involved in the vitamin D (vitD) metabolic pathway. Association of genetic polymorphisms in these two genes with 25-hyroxyvitamin D (25(OH)D) level has been reported in several studies. However, this association has been reported to be discrepant among populations from different ethnicities. Therefore, we aimed in this study to investigate association of the two major single nucleotide polymorphisms (SNP) in (rs4588 and rs7014) and a SNP (rs12794714) in in postmenopausal women in Saudi Arabia.
This study randomly selected 459 postmenopausal women (aged ≥50 years) of multiple ethnicities in Jeddah, Saudi Arabia. Blood samples were collected from all participating women for DNA extraction and for assessment of serum levels of total 25(OH)D, directly measured free 25(OH)D and other biochemical parameters. SNPs in selected vitD related genes (rs4588 in , c.1364G > T with transcript ID: NM_001204307.1 and rs7041 in , c.1353A > C with transcript ID NM_001204307.1 and rs12794714 in , c.177G > A with transcript ID NM_024514.4) were determined in DNA samples using Sanger DNA sequencing.
Minor allele frequency for rs4588, rs7041 and rs12794714 were 0.25, 0.44 and 0.42 respectively. Genotypes of rs7041 showed significant difference in total 25(OH)D level but not in free 25(O)D level (P = 0.023). In comparison, genotypes of rs4588 and rs12794714 did not show any significant difference neither in total nor in free 25(OH)D level. Post hoc test revealed that total 25(OH)D was lower in the rs7041 TT allele compared to the GG allele (P = 0.022). Chi-square test showed that vitD status was associated with rs7041 genotypes (P = 0.035). In addition, rs7041 minor alleles were found to have an association with vitD deficiency with a statistical significant odds ratio (>1) of 2.24 and 3.51 with P = 0.006 and P = 0.007 for TG and GG genotypes respectively.
The rs7041 SNP in was associated with total 25(OH)D level in postmenopausal women in Saudi Arabia, while rs4588 in and rs12794714 in did not show association with total 25(OH)D. Further studies exploring additional variants in vitD related genes are needed to understand genetic factors underlying vitD deficiency in Saudi population.
群体特异性成分（GC）和细胞色素P450家族2亚家族R成员1（CYP2R1）基因是维生素D（vitD）代谢途径中的关键基因之一。多项研究报道了这两个基因的遗传多态性与25-羟基维生素D（25(OH)D）水平的关联。然而，据报道，不同种族人群之间这种关联存在差异。因此，本研究旨在调查沙特阿拉伯绝经后女性中GC基因的两个主要单核苷酸多态性（SNP）（rs4588和rs7014）以及CYP2R1基因中的一个SNP（rs12794714）之间的关联。
本研究在沙特阿拉伯吉达随机选取了459名多种族的绝经后女性（年龄≥50岁）。采集所有参与研究女性的血样用于DNA提取以及评估血清总25(OH)D水平、直接测定的游离25(OH)D水平和其他生化参数。使用桑格DNA测序法在DNA样本中测定所选vitD相关基因的SNP（GC基因中的rs4588，c.1364G>T，转录本ID：NM_001204307.1；GC基因中的rs7041，c.1353A>C，转录本ID NM_001204307.1；CYP2R1基因中的rs12794714，c.177G>A，转录本ID NM_024514.4）。
rs4588、rs7041和rs12794714的次要等位基因频率分别为0.25、0.44和0.42。rs7041的基因型在总25(OH)D水平上存在显著差异，但在游离25(OH)D水平上无显著差异（P = 0.023）。相比之下，rs4588和rs12794714的基因型在总25(OH)D水平和游离25(OH)D水平上均未显示出任何显著差异。事后检验显示，与GG等位基因相比，rs7041的TT等位基因的总25(OH)D水平较低（P = 0.022）。卡方检验表明vitD状态与rs7041基因型相关（P = 0.035）。此外，发现rs7041次要等位基因与vitD缺乏有关，TG和GG基因型的统计显著优势比（>1）分别为2.24和3.51，P分别为0.006和0.007。
沙特阿拉伯绝经后女性中，GC基因的rs7041 SNP与总25(OH)D水平相关，而GC基因中的rs4588和CYP2R1基因中的rs12794714与总25(OH)D无关联。需要进一步研究探索vitD相关基因中的其他变异，以了解沙特人群中vitD缺乏的遗传因素。
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