Functional variants in MBL2 are associated with type 2 diabetes and pre-diabetes traits in Pima Indians and the old order Amish.
Functional variants in MBL2 are associated with type 2 diabetes and pre-diabetes traits in Pima Indians and the old order Amish.
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作者：
Muller YL;Hanson RL;Bian L;Mack J;Shi X;Pakyz R;Shuldiner AR;Knowler WC;Bogardus C;Baier LJ
MBL 2编码甘露糖结合凝集素，甘露糖结合凝集素是先天免疫系统中的关键参与者，最近发现在胰岛素抵抗和1型糖尿病和妊娠糖尿病的发展中发挥作用。为了评估MBL 2在糖尿病易感性中的作用，该基因在Pima印第安人人群中进行了分析，该人群2型糖尿病患病率较高。19个标签单核苷酸多态性（SNPs）基因分型的3,501个完整的皮马印第安人的人口为基础的样本，并选择SNPs进一步基因分型的独立样本的美洲原住民（n = 3,723）和旧秩序阿米什人（n = 486）的主题。两个变体，一个启动子SNP（rs 11003125），风险等位基因频率为0.77，Gly 54 Asp（rs 1800450），风险等位基因频率为0.83，与2型糖尿病在全遗传皮马印第安人（rs 1103125的优势比为1.30/拷贝G等位基因，P = 0.0007，rs 1800450的优势比为1.30/拷贝甘氨酸等位基因，P = 0.002，经年龄、性别、出生年份和家庭成员身份校正）。这些关联在一个独立的美洲原住民样本（1.19，P = 0.04，rs 11003125）和一个高加索人样本（1.51，P = 0.004，rs 1103125和2.38，P = 0.003，rs 1800450）中重复。在葡萄糖耐量正常的皮马印第安人中，Gly 54 Asp的糖尿病风险等位基因甘氨酸与静脉葡萄糖推注的急性胰岛素反应降低相关（P = 0.004，经年龄、性别、体脂百分比、生理胰岛素刺激下的葡萄糖处置和家庭成员身份调整）。我们的数据表明，MBL 2的功能变异有助于2型糖尿病的易感性在美洲原住民和旧秩序阿米什人。
MBL2 encodes the mannose-binding lectin, which is a key player in the innate immune system and has recently been found to play a role in insulin resistance and development of type 1 diabetes and gestational diabetes mellitus. To assess the role of MBL2 in diabetes susceptibility, this gene was analyzed in the Pima Indian population, which has a high prevalence of type 2 diabetes. Nineteen tag single nucleotide polymorphisms (SNPs) were genotyped in a population-based sample of 3,501 full-heritage Pima Indians, and selected SNPs were further genotyped in independent samples of Native American (n = 3,723) and Old Order Amish (n = 486) subjects. Two variants, a promoter SNP (rs11003125) at −550 bp with a risk allele frequency of 0.77 and a Gly54Asp (rs1800450) with a risk allele frequency of 0.83, were associated with type 2 diabetes in the full-heritage Pima Indians (odds ratio 1.30 per copy of the G allele for rs1103125, P = 0.0007, and 1.30 per copy of the glycine allele for rs1800450, P = 0.002, adjusted for age, sex, birth year, and family membership). These associations replicated in an independent Native American sample (1.19, P = 0.04, for rs11003125) and a Caucasian sample, the Old Order Amish (1.51, P = 0.004, for rs1103125 and 2.38, P = 0.003, for rs1800450). Among Pima Indians with normal glucose tolerance, the diabetes risk allele glycine of Gly54Asp was associated with a decreased acute insulin response to an intravenous glucose bolus infusion (P = 0.004, adjusted for age, sex, percent body fat, glucose disposal under physiological insulin stimulation, and family membership). Our data suggest that the functional variants in MBL2 contribute to type 2 diabetes susceptibility in both Native Americans and the Old Order Amish.
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影响因子：
30.8
作者：
Zeggini, Eleftheria;Scott, Laura J.;Saxena, Richa;Voight, Benjamin F.;Marchini, Jonathan L.;Hu, Tianle;de Bakker, Paul I. W.;Abecasis, Goncalo R.;Almgren, Peter;Andersen, Gitte;Ardlie, Kristin;Bostroem, Kristina Bengtsson;Bergman, Richard N.;Bonnycastle, Lori L.;Borch-Johnsen, Knut;Burtt, Noel P.;Chen, Hong;Chines, Peter S.;Daly, Mark J.;Deodhar, Parimal;Ding, Chia-Jen;Doney, Alex S. F.;Duren, William L.;Elliott, Katherine S.;Erdos, Michael R.;Frayling, Timothy M.;Freathy, Rachel M.;Gianniny, Lauren;Grallert, Harald;Grarup, Niels;Groves, Christopher J.;Guiducci, Candace;Hansen, Torben;Herder, Christian;Hitman, Graham A.;Hughes, Thomas E.;Isomaa, Bo;Jackson, Anne U.;Jorgensen, Torben;Kong, Augustine;Kubalanza, Kari;Kuruvilla, Finny G.;Kuusisto, Johanna;Langenberg, Claudia;Lango, Hana;Lauritzen, Torsten;Li, Yun;Lindgren, Cecilia M.;Lyssenko, Valeriya;Marvelle, Amanda F.;Meisinger, Christa;Midthjell, Kristian;Mohlke, Karen L.;Morken, Mario A.;Morris, Andrew D.;Narisu, Narisu;Nilsson, Peter;Owen, Katharine R.;Palmer, Colin N. A.;Payne, Felicity;Perry, John R. B.;Pettersen, Elin;Platou, Carl;Prokopenko, Inga;Qi, Lu;Qin, Li;Rayner, Nigel W.;Rees, Matthew;Roix, Jeffrey J.;Sandbaek, Anelli;Shields, Beverley;Sjogren, Marketa;Steinthorsdottir, Valgerdur;Stringham, Heather M.;Swift, Amy J.;Thorleifsson, Gudmar;Thorsteinsdottir, Unnur;Timpson, Nicholas J.;Tuomi, Tiinamaija;Tuomilehto, Jaakko;Walker, Mark;Watanabe, Richard M.;Weedon, Michael N.;Willer, Cristen J.;Illig, Thomas;Hveem, Kristian;Hu, Frank B.;Laakso, Markku;Stefansson, Kari;Pedersen, Oluf;Wareham, Nicholas J.;Barroso, Ines;Hattersley, Andrew T.;Collins, Francis S.;Groop, Leif;McCarthy, Mark I.;Boehnke, Michael;Altshuler, David
通讯作者：
Altshuler, David
影响因子：
7.7
作者：
Hanson, Robert L.;Bogardus, Clifton;Knowler, William C.
通讯作者：
Knowler, William C.
影响因子：
9.8
作者：
Almasy, L;Blangero, J
通讯作者：
Blangero, J
DOI：
10.1002/dmr.5610040508
发表时间：
1988-08-01
期刊：
DIABETES-METABOLISM REVIEWS
影响因子：
--
作者：
LILLIOJA, S;BOGARDUS, C
通讯作者：
BOGARDUS, C
影响因子：
9.8
作者：
Norman, RA;Tataranni, PA;Ravussin, E
通讯作者：
Ravussin, E