New polymorphism of ENPP1 (PC-1) is associated with increased risk of type 2 diabetes among obese individuals
New polymorphism of ENPP1 (PC-1) is associated with increased risk of type 2 diabetes among obese individuals
复制标题
DOI：
10.2337/db06-0191
复制
发表时间：
2006-09-01
期刊：
影响因子：
7.7
通讯作者：
Krolewski, Andrzej S.
中科院分区：
文献类型：
--
作者：
Bochenski, Jacek;Placha, Grzegorz;Krolewski, Andrzej S.
外核苷酸焦磷酸酶/磷酸二酯酶1（ENPP 1）的K121 Q多态性与2型糖尿病和肥胖相关。其他ENPP 1多态性影响这些表型的可能性很少受到关注。我们的目的是研究标记单核苷酸多态性（SNPs）和单倍型的连锁不平衡（LD）块包含K121 Q多态性与2型糖尿病在波兰人口，控制肥胖的任何影响。我们做了基因分型。426例2型糖尿病患者和370例对照者检测ENPP 1基因的7个SNPs。在总组中，2型糖尿病和肥胖均与任何SNP无显着相关。然而，在肥胖受试者中，两种SNI与2型糖尿病显著相关：K121 Q的Q等位基因（比值比1.6 [95%CI 1.003-2.6]）和rs 997509的T等位基因（4.7 [1.6-13.9]）。在LD区块中，4个SNP加上K121 Q多态性区分了6个单倍型，其中3个携带Q等位基因。有趣的是，rs 997509的T等位基因足以区分携带121 Q的单倍型，该单倍型与2型糖尿病的相关性显著高于其他两种单倍型（4.2 [1.3-13.5]）。另外两个携带121 Q的单倍型与2型糖尿病无关。总之，我们在内含子1中发现了一个新的SNP rs 997509，它与肥胖个体患2型糖尿病的风险密切相关。这种关联的分子机制尚不清楚。
The K121Q polymorphism in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is associated with type 2 diabetes and obesity. The possibility of other ENPP1 polymorphisms influencing these phenotypes has received little attention. Our aim was to examine the associations of tagging single nucleotide polymorphisms (SNPs) and haplotypes of the linkage disequilibrium (LD) block containing K121Q polymorphism with type 2 diabetes in a Polish population, controlling for any effect of obesity. We genotyped. 426 type 2 diabetic case and 370 control subjects for seven SNPs in ENPP1. In the total group, neither type 2 diabetes nor obesity was significantly associated with any SNP. However, in obese subjects, two SNIs were significantly associated with type 2 diabetes: the Q allele of K121Q (odds ratio 1.6 [95% Cl 1.003-2.6]) and T allele of rs997509 (4.7 [1.6-13.9]). In the LD block, four SNPs plus the K121Q polymorphism distinguished six haplotypes, three of which carried the Q allele. Interestingly, the T allele of rs997509 sufficed to distinguish a 121Q-carrying haplotype that was significantly more associated with type 2 diabetes than the other two (4.2 [1.3-13.5]). These other two 121Q-carrying haplotypes were not associated with type 2 diabetes. In conclusion, we found a new SNP, rs997509, in intron 1 that is strongly associated with risk of type 2 diabetes in obese individuals. The molecular mechanisms underlying this association are unknown.