Variation in Maturity-Onset Diabetes of the Young Genes Influence Response to Interventions for Diabetes Prevention.
Variation in Maturity-Onset Diabetes of the Young Genes Influence Response to Interventions for Diabetes Prevention.
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DOI：
10.1210/jc.2016-3429
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发表时间：
2017-08-01
期刊：
影响因子：
--
通讯作者：
Diabetes Prevention Program Research Group
中科院分区：
文献类型：
--
作者：
Billings LK;Jablonski KA;Warner AS;Cheng YC;McAteer JB;Tipton L;Shuldiner AR;Ehrmann DA;Manning AK;Dabelea D;Franks PW;Kahn SE;Pollin TI;Knowler WC;Altshuler D;Florez JC;Diabetes Prevention Program Research Group
引起年轻人成熟型糖尿病（MODY）的基因变异与糖尿病发病率和血糖特征有关。本研究旨在确定MODY基因的遗传变异是否会导致对胰岛素增敏干预的不同反应。这是一项多中心随机临床试验的二次分析，糖尿病预防计划（DPP），涉及27个美国学术机构。我们对DPP参与者中引起mody的基因中的22个错义和221个常见变异进行了基因分型。该研究包括2806名基因型DPP参与者，随机接受强化生活方式干预（n = 935）、二甲双胍（n = 927）或安慰剂（n = 944）。MODY基因变异与糖尿病发病率的关联，中位时间为3年，测量1年β细胞功能、胰岛素生成指数和口腔倾向指数。按治疗组进行分层分析，单核苷酸多态性×治疗相互作用显著（Pint < 0.05）。序列核关联试验检验了罕见错义变异和胰岛素原性状之间的关联。1年后，在二甲双胍组和生活方式组中，rs3212185 （HNF4A）的次要等位基因与β细胞功能的改善相关，而安慰剂组则没有；rs6719578的次要等位基因（NEUROD1）与二甲双胍组胰岛素分泌增加有关，而安慰剂组和生活方式组则没有。这些结果为MODY基因的遗传变异可能影响胰岛素增敏干预的反应提供了证据。通过β细胞功能和糖尿病发病率测量，MODY基因的遗传变异与糖尿病预防干预的反应有关。
Variation in genes that cause maturity-onset diabetes of the young (MODY) has been associated with diabetes incidence and glycemic traits. This study aimed to determine whether genetic variation in MODY genes leads to differential responses to insulin-sensitizing interventions. This was a secondary analysis of a multicenter, randomized clinical trial, the Diabetes Prevention Program (DPP), involving 27 US academic institutions. We genotyped 22 missense and 221 common variants in the MODY-causing genes in the participants in the DPP. The study included 2806 genotyped DPP participants randomized to receive intensive lifestyle intervention (n = 935), metformin (n = 927), or placebo (n = 944). Association of MODY genetic variants with diabetes incidence at a median of 3 years and measures of 1-year β-cell function, insulinogenic index, and oral disposition index. Analyses were stratified by treatment group for significant single-nucleotide polymorphism × treatment interaction (Pint < 0.05). Sequence kernel association tests examined the association between an aggregate of rare missense variants and insulinogenic traits. After 1 year, the minor allele of rs3212185 (HNF4A) was associated with improved β-cell function in the metformin and lifestyle groups but not the placebo group; the minor allele of rs6719578 (NEUROD1) was associated with an increase in insulin secretion in the metformin group but not in the placebo and lifestyle groups. These results provide evidence that genetic variation among MODY genes may influence response to insulin-sensitizing interventions. Genetic variation in MODY genes was associated with response to diabetes prevention interventions as measured by β-cell function and diabetes incidence.
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影响因子：
158.5
作者：
Knowler, WC;Barrett-Connor, E;Nathan, DM
通讯作者：
Nathan, DM
全基因组关联研究的荟萃分析确定了东亚人 2 型糖尿病的 8 个新位点
影响因子：
30.8
作者：
Cho, Yoon Shin;Chen, Chien-Hsiun;Hu, Cheng;Long, Jirong;Ong, Rick Twee Hee;Sim, Xueling;Takeuchi, Fumihiko;Wu, Ying;Go, Min Jin;Yamauchi, Toshimasa;Chang, Yi-Cheng;Kwak, Soo Heon;Ma, Ronald C. W.;Yamamoto, Ken;Adair, Linda S.;Aung, Tin;Cai, Qiuyin;Chang, Li-Ching;Chen, Yuan-Tsong;Gao, Yutang;Hu, Frank B.;Kim, Hyung-Lae;Kim, Sangsoo;Kim, Young Jin;Lee, Jeannette Jen-Mai;Lee, Nanette R.;Li, Yun;Liu, Jian Jun;Lu, Wei;Nakamura, Jiro;Nakashima, Eitaro;Ng, Daniel Peng-Keat;Tay, Wan Ting;Tsai, Fuu-Jen;Wong, Tien Yin;Yokota, Mitsuhiro;Zheng, Wei;Zhang, Rong;Wang, Congrong;So, Wing Yee;Ohnaka, Keizo;Ikegami, Hiroshi;Hara, Kazuo;Cho, Young Min;Cho, Nam H.;Chang, Tien-Jyun;Bao, Yuqian;Hedman, Asa K.;Morris, Andrew P.;McCarthy, Mark I.;Takayanagi, Ryoichi;Park, Kyong Soo;Jia, Weiping;Chuang, Lee-Ming;Chan, Juliana C. N.;Maeda, Shiro;Kadowaki, Takashi;Lee, Jong-Young;Wu, Jer-Yuarn;Teo, Yik Ying;Tai, E. Shyong;Shu, Xiao Ou;Mohlke, Karen L.;Kato, Norihiro;Han, Bok-Ghee;Seielstad, Mark
通讯作者：
Seielstad, Mark
影响因子：
30.8
作者：
Flannick J;Beer NL;Bick AG;Agarwala V;Molnes J;Gupta N;Burtt NP;Florez JC;Meigs JB;Taylor H;Lyssenko V;Irgens H;Fox E;Burslem F;Johansson S;Brosnan MJ;Trimmer JK;Newton-Cheh C;Tuomi T;Molven A;Wilson JG;O'Donnell CJ;Kathiresan S;Hirschhorn JN;Njølstad PR;Rolph T;Seidman JG;Gabriel S;Cox DR;Seidman CE;Groop L;Altshuler D
通讯作者：
Altshuler D
影响因子：
30.8
作者：
de Bakker, PIW;Yelensky, R;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
9.8
作者：
Li, Bingshan;Leal, Suzanne M.
通讯作者：
Leal, Suzanne M.