Gatto Nicole M, Sinsheimer Janet S, Cockburn Myles, Escobedo Loraine A, Bordelon Yvette, Ritz Beate
Center for Nutrition, Healthy Lifestyles & Disease Prevention, School of Public Health, Loma Linda University, United States.
Department of Human Genetics, UCLA, United States; Department of Biomathematics, UCLA, United States; Department of Biostatistics, UCLA, United States.
J Neurol Sci. 2015 May 15;352(1-2):88-93. doi: 10.1016/j.jns.2015.03.043. Epub 2015 Apr 7.
A high prevalence of vitamin D deficiency has been reported in Parkinson's disease (PD). Epidemiologic studies examining variability in genes involved in vitamin D metabolism have not taken into account level of exposure to ultraviolet radiation (UVR). We examined whether exposure to UVR (as a surrogate for vitamin D levels) and variations in the vitamin D receptor gene (VDR) are associated with PD.
Within a geographical information system (GIS) we linked participants' geocoded residential address data to ground level UV data to estimate historical exposure to UVR. Six SNPs in VDR were genotyped in non-Hispanic Caucasian subjects.
Average lifetime UVR exposure levels were >5000 Wh/m(2), which was higher than levels for populations in previous studies, and UVR exposure did not differ between cases and controls. Homozygotes for the rs731236 TT (major allele) genotype had a 31% lower risk of PD risk (OR=0.69; 95% CI=0.49, 0.98; p=0.04 for TT vs. TC+CC). The rs7975232 GG (minor allele) genotype was also associated with decreased risk of PD (OR=0.63; 95% CI=0.42, 0.93; p=0.02 for GG vs. TG+TT). The association between PD risk and a third locus, rs1544410 (BsmI), was not statistically significant after adjustment for covariates, although there was a trend for lower risk with the GG genotype.
This study provides initial evidence that VDR polymorphisms may modulate risk of PD in a population highly exposed to UVR throughout lifetime.
帕金森病(PD)患者中维生素D缺乏的患病率较高。研究维生素D代谢相关基因变异性的流行病学研究未考虑紫外线辐射(UVR)暴露水平。我们研究了UVR暴露(作为维生素D水平的替代指标)和维生素D受体基因(VDR)变异是否与PD相关。
在地理信息系统(GIS)中,我们将参与者经地理编码的居住地址数据与地面UV数据相链接,以估计历史UVR暴露情况。对非西班牙裔白人受试者的VDR中的6个单核苷酸多态性进行基因分型。
终生UVR平均暴露水平>5000 Wh/m²,高于先前研究中人群的水平,且病例组和对照组之间的UVR暴露无差异。rs731236 TT(主要等位基因)基因型的纯合子患PD的风险降低31%(OR = 0.69;95% CI = 0.49,0.98;TT与TC + CC相比,p = 0.04)。rs7975232 GG(次要等位基因)基因型也与PD风险降低相关(OR = 0.63;95% CI = 0.42,0.93;GG与TG + TT相比,p = 0.02)。尽管GG基因型有降低风险的趋势,但在调整协变量后,PD风险与第三个位点rs1544410(BsmI)之间的关联无统计学意义。
本研究提供了初步证据,表明在终生高度暴露于UVR的人群中,VDR基因多态性可能调节PD风险。