Takeuchi F, Ochiai Y, Serizawa M, Yanai K, Kuzuya N, Kajio H, Honjo S, Takeda N, Kaburagi Y, Yasuda K, Shirasawa S, Sasazuki T, Kato N
Department of Medical Ecology and Informatics, Research Institute, International Medical Center of Japan, Tokyo, Japan.
Department of Gene Diagnostics and Therapeutics, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
J Hum Genet. 2008;53(4):314-324. doi: 10.1007/s10038-008-0254-6. Epub 2008 Feb 8.
To systematically evaluate genetic susceptibility to type 2 diabetes (T2D) in "candidate" regions on chromosomes 1q, 3q and 12q, we examined disease association by using a total of 2,083 SNPs in two-step screening; a screening panel comprised 473 cases and 285 controls and an extended (or combined) panel involved 658 cases and 474 controls. For the total interval screened (40.9 Mb), suggestive evidence of association was provided for several annotated gene loci. For example, in the MCF2L2 gene on 3q, a significant association (a nominal P value of 0.00009) was observed when logistic regression analysis was performed for three associated SNPs (rs684846, rs35069869 and rs35368790) that belonged to different LD groups. Also, in the SLC15A4 gene on 12q, rs3765108 showed a marginally significant association with an overall estimated odds ratio of 0.79 (P=0.001). No significant association was found for known candidate gene loci on 3q, such as ADIPOQ and IGF2BP2. Using the available samples, we have observed disease associations of SNPs derived from two novel gene loci in the Japanese population through high-density searches of diabetes susceptibility in three chromosomal regions. Independent replication will clarify the etiological relevance of these genomic loci to T2D.
为了系统评估1号染色体长臂、3号染色体长臂和12号染色体长臂上“候选”区域对2型糖尿病（T2D）的遗传易感性，我们通过两步筛选共检测了2083个单核苷酸多态性（SNP）的疾病关联性；一个筛选组包括473例病例和285例对照，一个扩展（或合并）组包括658例病例和474例对照。对于所筛选的整个区间（40.9兆碱基），为几个注释基因座提供了关联性的提示性证据。例如，在3号染色体长臂上的MCF2L2基因中，对属于不同连锁不平衡（LD）组的三个关联SNP（rs684846、rs35069869和rs35368790）进行逻辑回归分析时，观察到显著关联（名义P值为0.00009）。此外，在12号染色体长臂上的SLC15A4基因中，rs3765108显示出边缘显著关联，总体估计比值比为0.79（P = 0.001）。在3号染色体长臂上的已知候选基因座，如ADIPOQ和IGF2BP2，未发现显著关联。利用现有样本，我们通过对三个染色体区域的糖尿病易感性进行高密度搜索，在日本人群中观察到了来自两个新基因座的SNP与疾病的关联性。独立重复研究将阐明这些基因组位点与T2D的病因学相关性。
