Aulchenko Yurii S, Vaessen Norbert, Heutink Peter, Pullen Jan, Snijders Pieter J L M, Hofman Albert, Sandkuijl Lodewijk A, Houwing-Duistermaat Jeanine J, Edwards Mark, Bennett Simon, Oostra Ben A, van Duijn Cornelia M
Department of Epidemiology & Biostatistics, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
Diabetes. 2003 Dec;52(12):3001-4. doi: 10.2337/diabetes.52.12.3001.
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 >1.17 (nominal P < 0.01). The strongest evidence for a type 2 diabetes locus was at marker D18S63 on chromosome 18p (LOD 2.3, P = 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.
多个基因与环境相互作用，导致了2型糖尿病易感性。我们在荷兰一个近期遗传隔离的人群中进行了全基因组搜索，以定位2型糖尿病易感基因。我们鉴定出79个患有2型糖尿病的核心家庭，这些家庭在13代内有亲缘关系，并进行了一次包含770个标记的全基因组扫描，以寻找共享的奠基者等位基因。26个标记产生的优势对数（LOD）得分>0.59（名义P<0.05），其中7个达到LOD得分>1.17（名义P<0.01）。2型糖尿病位点的最有力证据位于18号染色体短臂上的标记D18S63处（LOD 2.3，P = 0.0006）。使用额外的标记对该区域进行了进一步研究。对于其中一个标记（D18S1105），我们发现它与2型糖尿病有显著关联（优势比6.7 [95% CI 1.5 - 30.7]，对于97-bp等位基因，假设为显性模型，P = 0.005），当将分析限制在高BMI患者时，该关联增强（12.25 [2.1 - 71]，P = 0.003）。Parker等人之前曾提出高BMI患者18号染色体短臂上存在一个位点。我们的研究是首次证实该位点。
