A genonte-wide search for genes involved in type 2 diabetes in a recently genetically isolated population from the Netherlands

被引:19
作者
Aulchenko, YS
Vaessen, N
Heutink, P
Pullen, J
Snijders, PJLM
Hofman, A
Sandkuijl, LA
Honwin-Duistermaat, JJ
Edwards, M
Bennett, S
Oostra, BA
van Duijn, CM
机构
[1] Erasmus Med Ctr Rotterdam, Genet Epidemiol Unit, Dept Epidemiol & Biostat, NL-3000 DR Rotterdam, Netherlands
[2] RAS, Inst Cytol & Genet, SD, Novosibirsk, Russia
[3] Erasmus Med Ctr, Dept Clin Genet, Rotterdam, Netherlands
[4] Oxagen Ltd, Abingdon, Oxon, England
[5] Leiden Univ, Ctr Med, Leiden, Netherlands
关键词
D O I
10.2337/diabetes.52.12.3001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Multiple genes, interacting with the environment, contribute to the susceptibility to type 2 diabetes. We performed a genome-wide search to localize type 2 diabetes susceptibility genes in a recently genetically isolated population in the Netherlands. We identified 79 nuclear families with type 2 diabetes who were related within 13 generations and performed a 770-marker genome-wide scan search for shared founder alleles. Twenty-six markers yielded a logarithm of odds (LOD) score > 0.59 (nominal P < 0.05), of which 7 reached LOD scores >1.11 (nominal P < 0.01). The.strongest evidence for a type 2 diabetes locus was at marker D18S63 on chromosome 18p (LOD 2.3, F = 0.0006). This region was investigated further using additional markers. For one of these markers (D18S1105), we found a significant association with type 2 diabetes (odds ratio 6.7 [95% CI 1.5-30.7], P = 0.005 for the 97-bp allele, assuming a dominant model), which increased when limiting the analysis to patients with high BMI (12.25 [2.1-71], P = 0.003). A locus on chromosome 18p in patients with high BMI was suggested earlier by Parker et al. Our study is the first to confirm this locus.
引用
收藏
页码:3001 / 3004
页数:4
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