Qu Hui-Qi, Grant Struan F A, Bradfield Jonathan P, Kim Cecilia, Frackelton Edward, Hakonarson Hakon, Polychronakos Constantin
Departments of Pediatrics and Human Genetics, McGill University, Montreal, Québec, Canada.
Diabetes. 2008 Jul;57(7):1983-6. doi: 10.2337/db08-0270. Epub 2008 Apr 21.
To search for a possible association of type 1 diabetes with 10 validated type 2 diabetes loci, i.e., PPARG, KCNJ11, WFS1, HNF1B, IDE/HHEX, SLC30A8, CDKAL1, CDKN2A/B, IGF2BP2, and FTO/RPGRIP1L.
Two European population samples were studied: 1) one case-control cohort of 514 type 1 diabetic subjects and 2,027 control subjects and 2) one family cohort of 483 complete type 1 diabetic case-parent trios (total 997 affected). A total of 13 tag single nucleotide polymorphisms (SNPs) from the 10 type 2 diabetes loci were analyzed for type 1 diabetes association.
No association of type 1 diabetes was found with any of the 10 type 2 diabetes loci, and no age-at-onset effect was detected. By combined analysis using the Wellcome Trust Case-Control Consortium type 1 diabetes data, SNP rs1412829 in the CDKN2A/B locus bordered on significance (P = 0.039) (odds ratio 0.929 [95% CI 0.867-0.995]), which did not reach the statistical significance threshold adjusted for 13 tests (alpha = 0.00385).
This study suggests that the type 2 diabetes loci do not play any obvious role in type 1 diabetes genetic susceptibility. The distinct molecular mechanisms of the two diseases highlighted the importance of differentiation diagnosis and different treatment principles.
探寻1型糖尿病与10个已验证的2型糖尿病基因座（即PPARG、KCNJ11、WFS1、HNF1B、IDE/HHEX、SLC30A8、CDKAL1、CDKN2A/B、IGF2BP2以及FTO/RPGRIP1L）之间可能存在的关联。
对两个欧洲人群样本进行了研究：1）一个病例对照队列，包含514名1型糖尿病患者和2027名对照者；2）一个家系队列，包含483个完整的1型糖尿病病例-父母三联体（共997名患者）。对来自10个2型糖尿病基因座的总共13个标签单核苷酸多态性（SNP）进行1型糖尿病关联分析。
未发现1型糖尿病与10个2型糖尿病基因座中的任何一个存在关联，也未检测到发病年龄效应。通过使用威康信托病例对照协会的1型糖尿病数据进行联合分析，CDKN2A/B基因座中的SNP rs1412829接近显著水平（P = 0.039）（优势比为0.929 [95%置信区间0.867 - 0.995]），但未达到针对13次检验调整后的统计学显著阈值（α = 0.00385）。
本研究表明，2型糖尿病基因座在1型糖尿病遗传易感性中未发挥任何明显作用。这两种疾病不同的分子机制凸显了鉴别诊断和不同治疗原则的重要性。
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