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维生素D受体基因变异与哮喘

Variants in the vitamin D receptor gene and asthma.

作者信息

Wjst Matthias

机构信息

Gruppe Molekulare Epidemiologie, Institut für Epidemiologie, GSF - Forschungszentrum für Umwelt und Gesundheit, Ingolstädter Landstrasse 1, D-85758 Neuherberg / Munich, Germany.

出版信息

BMC Genet. 2005 Jan 15;6:2. doi: 10.1186/1471-2156-6-2.

Abstract

BACKGROUND

Early lifetime exposure to dietary or supplementary vitamin D has been predicted to be a risk factor for later allergy. Twin studies suggest that response to vitamin D exposure might be influenced by genetic factors. As these effects are primarily mediated through the vitamin D receptor (VDR), single base variants in this gene may be risk factors for asthma or allergy.

RESULTS

951 individuals from 224 pedigrees with at least 2 asthmatic children were analyzed for 13 SNPs in the VDR. There was no preferential transmission to children with asthma. In their unaffected sibs, however, one allele in the 5' region was 0.5-fold undertransmitted (p = 0.049), while two other alleles in the 3' terminal region were 2-fold over-transmitted (p = 0.013 and 0.018). An association was also seen with bronchial hyperreactivity against methacholine and with specific immunoglobulin E serum levels.

CONCLUSION

The transmission disequilibrium in unaffected sibs of otherwise multiple-affected families seem to be a powerful statistical test. A preferential transmission of vitamin D receptor variants to children with asthma could not be confirmed but raises the possibility of a protective effect for unaffected children.

摘要

背景

早年暴露于膳食或补充维生素D被预测为日后发生过敏的一个风险因素。双胞胎研究表明,对维生素D暴露的反应可能受遗传因素影响。由于这些效应主要通过维生素D受体(VDR)介导,该基因中的单碱基变异可能是哮喘或过敏的风险因素。

结果

对来自224个家系的951名个体进行分析,这些家系中至少有2名哮喘患儿,检测其VDR基因中的13个单核苷酸多态性(SNP)。未发现向哮喘患儿的优先传递。然而,在其未患病的同胞中,5'区域的一个等位基因传递不足0.5倍(p = 0.049),而3'末端区域的另外两个等位基因传递超过2倍(p = 0.013和0.018)。还发现与对乙酰甲胆碱的支气管高反应性以及特异性免疫球蛋白E血清水平有关联。

结论

在其他方面受累多个的家庭中未患病同胞的传递不平衡似乎是一种有效的统计学检验方法。维生素D受体变异向哮喘患儿的优先传递未能得到证实,但增加了对未患病儿童具有保护作用的可能性。

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