Diabetes：两个1型糖尿病致病基因

　　

生物通报道，美国费城儿童医院病理医学实验室、内分泌实验室、基因组学实验室、遗传学实验室和加拿大McGill大学人类遗传学实验室、加拿大Ottawa大学儿童健康中心的科学家近期在1型糖尿病的研究上取得新进展，科学家们在人类基因组上找到两个的1型糖尿易感基因转座子。相关的报道发表在10月7号最新出版的美国糖尿病学会期刊《Diabetes》上。

 

研究小组使用Illumina HumanHap550 BeadChip系统对563名1型糖尿病患者和1146名健康人群进行基因组学研究。

 

结果发现，有两个基因座UBASH3A与BACH2与1型糖尿病的易感性有密切的关联，据悉这两个基因与自体免疫性有极大的关联。UBSAH3A是位于21号染色体上的基因座，BACH2是位于6号染色体上的基因座，这两个基因在免疫细胞中十分活跃，与1型糖尿病的关系正在进一步的研究调查中。这两个基因座的具体功能还在进一步的研究中。

 

研究专家称，希望能深入了解1型糖尿病的遗传发病机制，这将有助于糖尿病的预防。诊断与治疗。

 

原文摘要：Follow up analysis of genome-wide association data identifies novel loci for type 1 diabetes

 

【Abstract】

Objective: Two recent genome wide association (GWA) studies have revealed novel loci for type 1 diabetes (T1D), a common multifactorial disease with a strong genetic component. To fully utilize the GWA data we had obtained by genotyping 563 T1D probands and 1,146 controls, as well as 483 case-parent trios, using the Illumina HumanHap550 BeadChip, we designed a full stage 2 study to capture other possible association signals.

 

Research Design and Methods: From our existing datasets, we selected 982 markers with P<0.05 in both GWA cohorts. Genotyping these in an independent set of 636 nuclear families with 974 affected offspring revealed 75 markers that also had P<0.05 in this third cohort. Among these, six SNPs in five novel loci also had P<0.05 in the Wellcome Trust Case-Control Consortium dataset and were further tested in 1,303 T1D probands from DCCT/EDIC plus 1,673 controls.

 

Results: Two markers (rs9976767 and rs3757247) remained significant after adjusting for the number of tests in this last cohort; they reside in UBASH3A (OR = 1.16; combined P = 2.33x10-8) and BACH2 (OR = 1.13; combined P = 1.25x10-6).

 

Conclusions: Evaluation of a large number of statistical GWA candidates in several independent cohorts has revealed additional loci that are associated with T1D. The two genes at these respective loci, UBASH3A and BACH2, are both biologically relevant to autoimmunity.