MTNR1B基因的变异会影响空腹血糖水平。
Variants in MTNR1B influence fasting glucose levels.
作者信息
Prokopenko Inga, Langenberg Claudia, Florez Jose C, Saxena Richa, Soranzo Nicole, Thorleifsson Gudmar, Loos Ruth J F, Manning Alisa K, Jackson Anne U, Aulchenko Yurii, Potter Simon C, Erdos Michael R, Sanna Serena, Hottenga Jouke-Jan, Wheeler Eleanor, Kaakinen Marika, Lyssenko Valeriya, Chen Wei-Min, Ahmadi Kourosh, Beckmann Jacques S, Bergman Richard N, Bochud Murielle, Bonnycastle Lori L, Buchanan Thomas A, Cao Antonio, Cervino Alessandra, Coin Lachlan, Collins Francis S, Crisponi Laura, de Geus Eco J C, Dehghan Abbas, Deloukas Panos, Doney Alex S F, Elliott Paul, Freimer Nelson, Gateva Vesela, Herder Christian, Hofman Albert, Hughes Thomas E, Hunt Sarah, Illig Thomas, Inouye Michael, Isomaa Bo, Johnson Toby, Kong Augustine, Krestyaninova Maria, Kuusisto Johanna, Laakso Markku, Lim Noha, Lindblad Ulf, Lindgren Cecilia M, McCann Owen T, Mohlke Karen L, Morris Andrew D, Naitza Silvia, Orrù Marco, Palmer Colin N A, Pouta Anneli, Randall Joshua, Rathmann Wolfgang, Saramies Jouko, Scheet Paul, Scott Laura J, Scuteri Angelo, Sharp Stephen, Sijbrands Eric, Smit Jan H, Song Kijoung, Steinthorsdottir Valgerdur, Stringham Heather M, Tuomi Tiinamaija, Tuomilehto Jaakko, Uitterlinden André G, Voight Benjamin F, Waterworth Dawn, Wichmann H-Erich, Willemsen Gonneke, Witteman Jacqueline C M, Yuan Xin, Zhao Jing Hua, Zeggini Eleftheria, Schlessinger David, Sandhu Manjinder, Boomsma Dorret I, Uda Manuela, Spector Tim D, Penninx Brenda Wjh, Altshuler David, Vollenweider Peter, Jarvelin Marjo Riitta, Lakatta Edward, Waeber Gerard, Fox Caroline S, Peltonen Leena, Groop Leif C, Mooser Vincent, Cupples L Adrienne, Thorsteinsdottir Unnur, Boehnke Michael, Barroso Inês, Van Duijn Cornelia, Dupuis Josée, Watanabe Richard M, Stefansson Kari, McCarthy Mark I, Wareham Nicholas J, Meigs James B, Abecasis Gonçalo R
机构信息
[1] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. [2] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [3] These authors contributed equally to this work.
出版信息
Nat Genet. 2009 Jan;41(1):77-81. doi: 10.1038/ng.290. Epub 2008 Dec 7.
To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.
为了识别与空腹血糖浓度相关的此前未知的基因位点，我们在涉及总计36610名欧洲裔个体的十项全基因组关联扫描中检查了主要的关联信号。编码褪黑素受体1B（MTNR1B）的基因中的变异在所有十项研究中均与空腹血糖持续相关。在rs10830963处观察到最强信号，其中每个G等位基因（在HapMap CEU中的频率为0.30）与空腹血糖水平升高0.07（95%可信区间=0.06 - 0.08）mmol/l相关（P = 3.2×10⁻⁵⁰），并且通过稳态模型评估（HOMA - B，P = 1.1×10⁻¹⁵）测量显示β细胞功能降低。在一项对总计18236例病例和64453例对照的13项病例对照研究的荟萃分析中，相同的等位基因与2型糖尿病风险增加相关（优势比 = 1.09（1.05 - 1.12），每个G等位基因P = 3.3×10⁻⁷）。我们的分析还证实了此前空腹血糖与G6PC2（rs560887，P = 1.1×10⁻⁵⁷）和GCK（rs4607517，P = 1.0×10⁻²⁵）基因座处的变异之间的关联。
Zotero 插件