Lyon Helen N, Florez Jose C, Bersaglieri Todd, Saxena Richa, Winckler Wendy, Almgren Peter, Lindblad Ulf, Tuomi Tiinamaija, Gaudet Daniel, Zhu Xiaofeng, Cooper Richard, Ardlie Kristin G, Daly Mark J, Altshuler David, Groop Leif, Hirschhorn Joel N
Division of Genetics, Children's Hospital Boston, Enders 561, 300 Longwood Ave., Boston, MA 02115, USA.
Diabetes. 2006 Nov;55(11):3180-4. doi: 10.2337/db06-0407.
The common missense single nucleotide polymorphism (SNP) K121Q in the ectoenzyme nucleotide pyrophosphate phosphodiesterase (ENPP1) gene has recently been associated with type 2 diabetes in Italian, U.S., and South-Asian populations. A three-SNP haplotype, including K121Q, has also been associated with obesity and type 2 diabetes in French and Austrian populations. We set out to confirm these findings in several large samples. We genotyped the haplotype K121Q (rs1044498), rs1799774, and rs7754561 in 8,676 individuals of European ancestry with and without type 2 diabetes, in 1,900 obese and 930 lean individuals of European ancestry from the U.S. and Poland, and in 1,101 African-American individuals. Neither the K121Q missense polymorphism nor the putative risk haplotype were significantly associated with type 2 diabetes or BMI. Two SNPs showed suggestive evidence of association in a meta-analysis of our European ancestry samples. These SNPs were rs7754561 with type 2 diabetes (odds ratio for the G-allele, 0.85 [95% CI 0.78-0.92], P = 0.00003) and rs1799774 with BMI (homozygotes of the delT-allele, 0.6 [0.42-0.88], P = 0.007). However, these findings are not supported by other studies. We did not observe a reproducible association between these three ENPP1 variants and BMI or type 2 diabetes.
胞外核苷酸焦磷酸磷酸二酯酶（ENPP1）基因常见的错义单核苷酸多态性（SNP）K121Q最近在意大利、美国和南亚人群中被发现与2型糖尿病有关。一种包含K121Q的三SNP单倍型在法国和奥地利人群中也与肥胖和2型糖尿病有关。我们着手在几个大样本中证实这些发现。我们对8676名有或无2型糖尿病的欧洲血统个体、1900名来自美国和波兰的肥胖及930名瘦的欧洲血统个体以及1101名非裔美国人进行了K121Q（rs1044498）、rs1799774和rs7754561单倍型基因分型。无论是K121Q错义多态性还是假定的风险单倍型均与2型糖尿病或体重指数无显著关联。在对我们欧洲血统样本的荟萃分析中，有两个SNP显示出提示性的关联证据。这些SNP分别是与2型糖尿病相关的rs7754561（G等位基因的优势比为0.85[95%可信区间0.78 - 0.92]，P = 0.00003）以及与体重指数相关的rs1799774（delT等位基因纯合子，0.6[0.42 - 0.88]，P = 0.007）。然而，其他研究并不支持这些发现。我们未观察到这三个ENPP1变体与体重指数或2型糖尿病之间存在可重复的关联。
