Genome-wide search for type 2 diabetes in Japanese affected sib-pails confirms susceptibility genes on 3q, 15q, and 20q and identifies two new candidate loci on 7p and 11p
Genome-wide search for type 2 diabetes in Japanese affected sib-pails confirms susceptibility genes on 3q, 15q, and 20q and identifies two new candidate loci on 7p and 11p
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DOI：
10.2337/diabetes.51.4.1247
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发表时间：
2002-04-01
期刊：
影响因子：
7.7
通讯作者：
Froguel, P
中科院分区：
文献类型：
--
作者：
Mori, Y;Otabe, S;Froguel, P
导致日本人群易患2型糖尿病的遗传背景在很大程度上是未知的。因此，我们对来自159个家庭的359名受影响的个体进行了10 cM的全基因组扫描，获得了224对日本血统的受影响同胞。在整个人群中进行的非参数多点连锁分析显示在11 p13-p12上存在一个提示性连锁区域（最大比值分数对数[MLS] 3.08，接近Pax 6）和7个潜在相关区域（MLS >1.17）位于1 p36-p32、2 q34、3q 26-q28、6p 23、7 p22-p21、15 q13-q21和20 q12-q13（靠近肝细胞核因子-4 α [HNF-4 α]基因）。根据最大BMI和早期诊断年龄进行的亚组分析增加了与2型糖尿病在7 p22-p21（MLS 3.51）、15 q13-q21（MLS 3.91）和20 q12-q13（MLS 2.32）的联系的提示性证据。这些结果支持了先前在其他人群中发现的染色体3q，15 q和20 q上的连锁指示，并确定了7 p和11 p上的两个新的潜在基因座，可能赋予日本人群2型糖尿病的遗传风险。
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.