Abstract:
Vitamin D deficiency (VDD) is widespread in the Arab world despite ample sunshine throughout the year. In our previous study, lifestyle and socio-demographic factors could explain only 45% of variability in vitamin D levels in Kuwaiti adolescents, suggesting that genetics might contribute to VDD in this region. Single nucleotide polymorphisms (SNP) in the 25-hydroxylase (CYP2R1) and the GC globulin (GC) genes have been reported to affect vitamin D levels in various ethnic groups in adults. In this study, we investigated the association of two SNPs from GC (rs4588 and rs7041) and three SNPs from CYP2R1 (rs10741657, rs11023374 and rs12794714) with vitamin D levels and VDD in a nationally representative sample of adolescents of Arab ethnicity from Kuwait. Multivariable linear regression, corrected for age, sex, parental education, governorate, body mass index, and exposure to sun, demonstrated that each of the 5 study variants showed significant associations with plasma 25(OH)D levels in one or more of the additive, recessive, and dominant genetic models - the rs10741657 under all the three models, rs12794714 under both the additive and recessive models, rs7041 under the recessive model; and rs4588 and rs11023374 under the dominant model. Minor alleles at rs4588 (T), rs7041 (A), rs11023374 (C), and rs12794714 (A) led to a decrease in plasma 25(OH)D levels - rs4588:[β (95%CI) = -4.522 (-8.66,-0.38); p=0.033]; rs7041:[β (95%CI) = -6.139 (-11.12,-1.15); p=0.016]; rs11023374:[β (95%CI) = -4.296 (-8.18,-0.40); p=0.031]; and rs12794714:[β (95%CI) = -3.498 (-6.27,-0.72); p=0.014]. Minor allele A at rs10741657 was associated with higher levels of plasma 25(OH)D levels [β (95%CI) = 4.844 (1.62,8.06); p=0.003)] and lower odds of vitamin D deficiency (OR 0.40; p=0.002). These results suggest that the CYP2R1 and GC SNP variants are partly responsible for the high prevalence of VDD in Kuwait. Genotyping these variants may be considered for the prognosis of VDD in Kuwait.
摘要:
尽管全年阳光充足,但维生素D缺乏症(VDD)在阿拉伯世界仍然很普遍。在我们之前的研究中,生活方式和社会人口因素只能解释科威特青少年维生素D水平变化的45%,这表明遗传学可能有助于该地区的VDD。据报道,25-羟化酶(CYP2R1)和GC球蛋白(GC)基因中的单核苷酸多态性(SNP)会影响成人各个种族的维生素D水平。在这项研究中,我们调查了来自科威特的具有全国代表性的阿拉伯裔青少年样本中来自GC的2个SNP(rs4588和rs7041)和来自CYP2R1的3个SNP(rs10741657,rs11023374和rs12794714)与维生素D水平和VDD的关联.多变量线性回归,纠正年龄,性别,父母教育,省,身体质量指数,暴露在阳光下,证明了5种研究变体中的每一种都与一种或多种添加剂中的血浆25(OH)D水平显着相关,隐性,和显性遗传模型-所有三个模型下的rs10741657,rs12794714在加法和隐性模型下,隐性模型下的rs7041;显性模型下的rs4588和rs11023374。rs4588(T)的次要等位基因,rs7041(A),rs11023374(C),和rs12794714(A)导致血浆25(OH)D水平降低-rs4588:[β(95CI)=-4.522(-8.66,-0.38);p=0.033];rs7041:[β(95CI)=-6.139(-11.12,-1.15);p=0.016];rs11023374:[β(958.72)-4p=0.rs10741657的次要等位基因A与较高的血浆25(OH)D水平[β(95CI)=4.844(1.62,8.06);p=0.003]和较低的维生素D缺乏几率相关(OR0.40;p=0.002)。这些结果表明,CYP2R1和GCSNP变体是科威特VDD高流行的部分原因。对这些变体进行基因分型可考虑用于科威特VDD的预后。