Aulchenko Yurii S, Pullen Jan, Kloosterman Wigard P, Yazdanpanah Mojgan, Hofman Albert, Vaessen Norbert, Snijders Pieter J L M, Zubakov Dmitry, Mackay Ian, Olavesen Mark, Sidhu Balbinder, Smith Vicki E, Carey Alisoun, Berezikov Eugene, Uitterlinden André G, Plasterk Ronald H A, Oostra Ben A, van Duijn Cornelia M
Department of Epidemiology and Biostatistics, Erasmus Medical Centre Rotterdam, Postbus 2040, 3000 CA Rotterdam, Netherlands.
Diabetes. 2007 Dec;56(12):3020-6. doi: 10.2337/db07-0338. Epub 2007 Sep 5.
To identify the type 2 diabetes gene located at chromosome 18p11.
We investigated the region in a young genetically isolated population by genotyping 34 single nucleotide polymorphisms (SNPs) in 78 case subjects and 101 control subjects. Two SNPs were selected and followed up in two cohorts. The first cohort came from a general Dutch population. In this cohort, association with type 2 diabetes was investigated using 616 type 2 diabetic case subjects and 2,890 control subjects; association with oral glucose tolerance test data was performed in 361 normoglycemic people. Association with fat distribution was studied in the second replication cohort, consisting of 836 people from the genetically isolated population.
At the initial step, we found that the common C allele of SNP rs3745012 was associated with type 2 diabetes (odds ratio 2.01, P = 0.03). This SNP is located at the 3' untranslated region of the LPIN2 gene, which is a plausible candidate for type 2 diabetes and obesity. In the cohort from the general Dutch population, we demonstrated that rs3745012 interacts with BMI in determination of type 2 diabetes: whereas in subjects with high BMI, the common C allele is associated with type 2 diabetes, the same allele exhibits a neutral or protective effect in lean subjects (P = 0.05 overall effect, P = 0.02 interaction). Most remarkably, rs3745012 strongly affected composite insulin sensitivity index (P = 0.006 for overall effect, P = 0.004 for interaction). In the second replication cohort, we found that the allele C of rs3745012 increases trunk-to-legs fat mass ratio (P = 0.001) and may affect other fat-related measurements.
rs3745012 SNP of the LPIN2 gene is associated with type 2 diabetes and fat distribution.
鉴定位于18号染色体p11区域的2型糖尿病基因。
我们通过对78例病例受试者和101例对照受试者的34个单核苷酸多态性（SNP）进行基因分型，对一个年轻的遗传隔离人群中的该区域进行了研究。选择了两个SNP并在两个队列中进行随访。第一个队列来自荷兰普通人群。在这个队列中，使用616例2型糖尿病病例受试者和2890例对照受试者研究与2型糖尿病的关联；在361例血糖正常的人群中进行了与口服葡萄糖耐量试验数据的关联研究。在由836名来自遗传隔离人群的个体组成的第二个重复队列中研究了与脂肪分布的关联。
在初始阶段，我们发现SNP rs3745012的常见C等位基因与2型糖尿病相关（优势比2.01，P = 0.03）。该SNP位于LPIN2基因的3'非翻译区，这是2型糖尿病和肥胖的一个合理候选基因。在来自荷兰普通人群的队列中，我们证明rs3745012在2型糖尿病的决定中与BMI相互作用：在高BMI受试者中，常见C等位基因与2型糖尿病相关，而在瘦受试者中，相同等位基因表现出中性或保护作用（总体效应P = 0.05，交互作用P = 0.02）。最显著的是，rs3745012强烈影响复合胰岛素敏感性指数（总体效应P = 0.006，交互作用P = 0.004）。在第二个重复队列中，我们发现rs3745012的C等位基因增加了躯干与腿部脂肪量比（P = 0.001），并可能影响其他与脂肪相关的测量指标。
LPIN2基因的rs3745012 SNP与2型糖尿病和脂肪分布相关。
