Mori Yasumichi, Otabe Shuichi, Dina Christian, Yasuda Kazuki, Populaire Céline, Lecoeur Cécile, Vatin Vincent, Durand Emmanuelle, Hara Kazuo, Okada Terumasa, Tobe Kazuyuki, Boutin Philippe, Kadowaki Takashi, Froguel Philippe
Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Diabetes. 2002 Apr;51(4):1247-55. doi: 10.2337/diabetes.51.4.1247.
The genetic background that predisposes the Japanese population to type 2 diabetes is largely unknown. Therefore, we conducted a 10-cM genome-wide scan for type 2 diabetes traits in the 359 affected individuals from 159 families, yielding 224 affected sib-pairs of Japanese origin. Nonparametric multipoint linkage analyses performed in the whole population showed one suggestive linked region on 11p13-p12 (maximum logarithm of odds score [MLS] 3.08, near Pax6) and seven potentially linked regions (MLS >1.17) at 1p36-p32, 2q34, 3q26-q28, 6p23, 7p22-p21, 15q13-q21, and 20q12-q13 (near the gene for hepatocyte nuclear factor-4alpha [HNF-4alpha]). Subset analyses according to maximal BMI and early age at diagnosis added suggestive evidence of linkage with type 2 diabetes at 7p22-p21 (MLS 3.51), 15q13-q21 (MLS 3.91), and 20q12-q13 (MLS 2.32). These results support previous indication for linkage found on chromosome 3q, 15q, and 20q in other populations and identifies two new potential loci on 7p and 11p that may confer genetic risk for type 2 diabetes in the Japanese population.
导致日本人群易患2型糖尿病的遗传背景在很大程度上尚不清楚。因此，我们对来自159个家庭的359名2型糖尿病患者进行了10厘摩（cM）全基因组扫描，得到了224对日本裔患病同胞对。在整个人群中进行的非参数多点连锁分析显示，在11p13 - p12上有一个提示性连锁区域（最大优势对数得分[MLS] 3.08，靠近Pax6），在1p36 - p32、2q34、3q26 - q28、6p23、7p22 - p21、15q13 - q21和20q12 - q13（靠近肝细胞核因子4α[HNF - 4α]基因）有七个潜在连锁区域（MLS >1.17）。根据最大体重指数（BMI）和诊断时的早期年龄进行的亚组分析增加了在7p22 - p21（MLS 3.51）、15q13 - q21（MLS 3.91）和20q12 - q13（MLS 2.32）与2型糖尿病连锁的提示性证据。这些结果支持了先前在其他人群中在3号染色体、15号染色体和20号染色体上发现的连锁迹象，并确定了7号染色体和11号染色体上两个新的潜在基因座，它们可能赋予日本人群2型糖尿病的遗传风险。
