Evidence for genetic regulation of vitamin D status in twins with multiple sclerosis.
Evidence for genetic regulation of vitamin D status in twins with multiple sclerosis.
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DOI：
10.1093/ajcn/88.2.441
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发表时间：
2008-08
期刊：
影响因子：
--
通讯作者：
Ebers GC
中科院分区：
文献类型：
--
作者：
Orton SM;Morris AP;Herrera BM;Ramagopalan SV;Lincoln MR;Chao MJ;Vieth R;Sadovnick AD;Ebers GC
背景：多发性硬化症（MS）的风险由基因和环境共同决定。MS最显著的特征之一是其地理分布，特别是在阳光照射量低的地区MS频率高的模式，这是维生素D合成的主要诱导物。最近的流行病学，实验和临床证据支持低环境供应的维生素D在介导MS易感性增加中的作用。我们1）检查了血清25-羟基维生素D [25（OH）D]浓度和MS状态的相关性，2）评估了血清25（OH）D浓度的遗传贡献，并测试了其与2个候选基因[维生素D受体和1-α-羟化酶（CYP 27 B1）]。设计图：我们使用了双胞胎研究的方法，包括成人对确定从纵向人口为基础的加拿大合作项目遗传易感性MS。单卵（MZ; n = 40）和双卵（DZ; n = 59）对，一致和不一致的MS，进行了研究。冬末血清25（OH）D浓度测定放射免疫法，基因型进行了评估单核苷酸多态性（SNP）分析。结果如下：MS-一致性配对中血清25（OH）D浓度高度相关（r = 0.83，P < 0.001），但经Logistic回归分析，其与患病无显著相关性（P = 0.4）。MZ组25（OH）D浓度的组内相关性显著更高（MZ组r：0.71 > DZ组r：0.32，P = 0.006）。观察到2种CYP 27 B1 SNP变异体与25（OH）D浓度显著相关。结论：研究结果表明，重要的遗传影响调节季节性循环25（OH）D浓度的MS双胞胎。
Background: Multiple sclerosis (MS) risk is determined by both genes and environment. One of the most striking features of MS is its geographic distribution, particularly the pattern of high MS frequency in areas with low sunlight exposure, the main inducer of vitamin D synthesis. Recent epidemiologic, experimental, and clinical evidence support an effect for low environmental supplies of vitamin D in mediating an increased susceptibility to MS. Objectives: We 1) examined the association of serum 25-hydroxy-vitaminD [25(OH)D] concentrations and MS status and 2) assessed the genetic contribution to serum 25(OH)D concentrations and tested for its association with genetic variants in 2 candidate genes [vitamin D receptor and 1-α-hydroxylase (CYP27B1)]. Design: We used a twin study approach, comprising adult pairs identified from the longitudinal population-based Canadian Collaborative Project on Genetic Susceptibility to MS. Monozygotic (MZ; n = 40) and dizygotic (DZ; n = 59) pairs, both concordant and discordant for MS, were studied. End-of-winter serum 25(OH)D concentrations were measured by radioimmunoassay, and genotypes were assessed by single nucleotide polymorphism (SNP) assay. Results: Serum concentrations of 25(OH)D were highly correlated in MS-concordant pairs (r = 0.83, P < 0.001), but they were not significantly associated with having the disease (P = 0.4) when analyzed by logistic regression. Intraclass correlation for 25(OH)D concentration was significantly greater in MZ pairs (MZ, r: 0.71 > DZ r: 0.32, P = 0.006). Significant associations of 2 CYP27B1 SNP variants and 25(OH)D concentrations were observed. Conclusion: The findings indicate important genetic influences on regulation of seasonal circulating 25(OH)D concentrations in MS twins.
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DOI：
10.1016/j.jsbmb.2006.12.096
发表时间：
2007-03-01
影响因子：
4.1
作者：
Eyles, D.;Almeras, L.;Feron, F.
通讯作者：
Feron, F.
影响因子：
--
作者：
GOLDBERG, P
通讯作者：
GOLDBERG, P
影响因子：
6.3
作者：
Goldacre, MJ;Seagroatt, V;Acheson, ED
通讯作者：
Acheson, ED
影响因子：
6.2
作者：
Hunter, D;De Lange, M;Spector, TD
通讯作者：
Spector, TD
DOI：
10.1177/1352458506072666
发表时间：
2007-06-01
期刊：
MULTIPLE SCLEROSIS
影响因子：
--
作者：
Barnes, M. S.;Bonham, M. P.;Wallace, J. M. W.
通讯作者：
Wallace, J. M. W.