Smyth Deborah J, Cooper Jason D, Bailey Rebecca, Field Sarah, Burren Oliver, Smink Luc J, Guja Cristian, Ionescu-Tirgoviste Constantin, Widmer Barry, Dunger David B, Savage David A, Walker Neil M, Clayton David G, Todd John A
Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK.
Nat Genet. 2006 Jun;38(6):617-9. doi: 10.1038/ng1800. Epub 2006 May 14.
In this study we report convincing statistical support for a sixth type 1 diabetes (T1D) locus in the innate immunity viral RNA receptor gene region IFIH1 (also known as mda-5 or Helicard) on chromosome 2q24.3. We found the association in an interim analysis of a genome-wide nonsynonymous SNP (nsSNP) scan, and we validated it in a case-control collection and replicated it in an independent family collection. In 4,253 cases, 5,842 controls and 2,134 parent-child trio genotypes, the risk ratio for the minor allele of the nsSNP rs1990760 A --> G (A946T) was 0.86 (95% confidence interval = 0.82-0.90) at P = 1.42 x 10(-10).
在本研究中，我们报告了令人信服的统计学证据，支持位于2号染色体2q24.3上的天然免疫病毒RNA受体基因区域IFIH1（也称为mda-5或Helicard）中存在第六个1型糖尿病（T1D）位点。我们在全基因组非同义单核苷酸多态性（nsSNP）扫描的中期分析中发现了这种关联，并在病例对照样本集中进行了验证，还在一个独立的家系样本集中进行了重复验证。在4253例病例、5842例对照以及2134个亲子三联体基因型中，nsSNP rs1990760 A→G（A946T）的次要等位基因的风险比为0.86（95%置信区间=0.82 - 0.90），P值为1.42×10⁻¹⁰。
