Strong parent-of-origin effects in the association of KCNQ1 variants with type 2 diabetes in American Indians.
Strong parent-of-origin effects in the association of KCNQ1 variants with type 2 diabetes in American Indians.
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作者：
Hanson RL;Guo T;Muller YL;Fleming J;Knowler WC;Kobes S;Bogardus C;Baier LJ
在冰岛人群中观察到了与2型糖尿病相关的几种遗传变异的父母效应，包括KLF14(Rs4731702)、MOB2(Rs2334499)和KCNQ1(rs2237892、rs231362)。我们分析了这些变异以及之前全基因组关联研究(rs2237895，rs2299620)中发现的KCNQ1中另外两个变异的父母效应，研究对象是来自4549个核心家庭的7351名皮马印度人；34%的参与者患有糖尿病。在287名血糖正常的人中，通过静脉葡萄糖耐量试验测量了急性胰岛素分泌。在统计学上有显著意义(P<；0.05)在所有变异中，父母的起源效应都与2型糖尿病相关。C等位基因与母亲来源的糖尿病相关(OR=1.92；P=4.1×10−12)，与父亲来源的糖尿病无关联(OR=0.93；P=0.47；P=9.9×10−6)。母体来源的C等位基因也与胰岛素分泌减少28%相关(P=0.002)。这项研究证实了KLF14、MOB2和KCNQ1基因变异与2型糖尿病相关的父母来源效应。在皮马印第安人中，母体来源的KCNQ1变异的影响似乎是通过胰岛素分泌减少来调节的，并且特别强烈，占糖尿病易感性变异的4%。
Parent-of-origin effects were observed in an Icelandic population for several genetic variants associated with type 2 diabetes, including those in KLF14 (rs4731702), MOB2 (rs2334499), and KCNQ1 (rs2237892, rs231362). We analyzed parent-of-origin effects for these variants, along with two others in KCNQ1 identified in previous genome-wide association studies (rs2237895, rs2299620), in 7,351 Pima Indians from 4,549 nuclear families; 34% of participants had diabetes. In a subset of 287 normoglycemic individuals, acute insulin secretion was measured by an intravenous glucose tolerance test. Statistically significant (P < 0.05) parent-of-origin effects were seen for association with type 2 diabetes for all variants. The strongest effect was seen at rs2299620 in KCNQ1; the C allele was associated with increased diabetes when maternally derived (odds ratio [OR], 1.92; P = 4.1 × 10−12), but not when paternally derived (OR, 0.93; P = 0.47; P = 9.9 × 10−6 for difference in maternal and paternal effects). A maternally derived C allele also was associated with a 28% decrease in insulin secretion (P = 0.002). This study confirms parent-of-origin effects in the association with type 2 diabetes for variants in KLF14, MOB2, and KCNQ1. In Pima Indians, the effect of maternally derived KCNQ1 variants appears to be mediated through decreased insulin secretion and is particularly strong, accounting for 4% of the variance in liability to diabetes.
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影响因子：
7.7
作者：
Dabelea, D;Hanson, RL;Knowler, WC
通讯作者：
Knowler, WC
影响因子：
3.7
作者：
van Vliet-Ostaptchouk JV;van Haeften TW;Landman GW;Reiling E;Kleefstra N;Bilo HJ;Klungel OH;de Boer A;van Diemen CC;Wijmenga C;Boezen HM;Dekker JM;van 't Riet E;Nijpels G;Welschen LM;Zavrelova H;Bruin EJ;Elbers CC;Bauer F;Onland-Moret NC;van der Schouw YT;Grobbee DE;Spijkerman AM;van der A DL;Simonis-Bik AM;Eekhoff EM;Diamant M;Kramer MH;Boomsma DI;de Geus EJ;Willemsen G;Slagboom PE;Hofker MH;'t Hart LM
通讯作者：
't Hart LM
影响因子：
7.7
作者：
Müssig K;Staiger H;Machicao F;Kirchhoff K;Guthoff M;Schäfer SA;Kantartzis K;Silbernagel G;Stefan N;Holst JJ;Gallwitz B;Häring HU;Fritsche A
通讯作者：
Fritsche A
影响因子：
3.2
作者：
Chang, Yi-Cheng;Chiu, Yen-Feng;Chuang, Lee-Ming
通讯作者：
Chuang, Lee-Ming
影响因子：
1.8
作者：
Sun, L;Wilder, K;McPeek, MS
通讯作者：
McPeek, MS