Genetic Determinants of Glycemic Traits and the Risk of Gestational Diabetes Mellitus.
Genetic Determinants of Glycemic Traits and the Risk of Gestational Diabetes Mellitus.
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作者：
Powe CE;Nodzenski M;Talbot O;Allard C;Briggs C;Leya MV;Perron P;Bouchard L;Florez JC;Scholtens DM;Lowe WL Jr;Hivert MF
许多常见的基因多态与血糖性状和2型糖尿病(T2D)相关，但对妊娠期血糖性状的遗传决定因素的了解有限。我们在一般人群中测试了已知与血糖性状和T2D相关的基因变异，以确定与妊娠期血糖性状和妊娠期糖尿病(GDM)的相关性。两组受试者在怀孕24-32周时接受了口服葡萄糖耐量测试，这两组受试者分别是妊娠和生长中的葡萄糖调节遗传学[Gen3G]和高血糖和不良妊娠结局[HAPO]。我们利用在非妊娠个体研究中发现的变异，建立了空腹血糖和胰岛素升高、胰岛素分泌和敏感性降低以及T2D的遗传风险评分(GRS)。我们测试了这些GRS、孕期血糖特征和妊娠期糖尿病之间的关系。在两个队列中，空腹血糖GRS与空腹血糖密切相关。在有胰岛素测量的Gen3G中，胰岛素分泌和敏感性GRS也与这些特征显著相关。空腹胰岛素GRS与空腹胰岛素(Gen3G)或C肽(HAPO)相关性较弱。在HAPO(207例GDM患者)中，所有5个GRS(T2D、空腹血糖、空腹胰岛素、胰岛素分泌和胰岛素敏感性)均与GDM显著相关。在Gen3G(43例GDM病例受试者)中，T2D和胰岛素分泌GRS都与GDM相关；其他GRS的效应大小与HAPO相似。因此，尽管妊娠期间血糖生理发生了深刻的变化，但在怀孕期间发现的空腹血糖、空腹胰岛素、胰岛素分泌和胰岛素敏感性等遗传决定因素会影响妊娠期糖尿病的风险。
Many common genetic polymorphisms are associated with glycemic traits and type 2 diabetes (T2D), but knowledge about genetic determinants of glycemic traits in pregnancy is limited. We tested genetic variants known to be associated with glycemic traits and T2D in the general population for associations with glycemic traits in pregnancy and gestational diabetes mellitus (GDM). Participants in two cohorts (Genetics of Glucose regulation in Gestation and Growth [Gen3G] and Hyperglycemia and Adverse Pregnancy Outcome [HAPO]) underwent oral glucose tolerance testing at 24–32 weeks’ gestation. We built genetic risk scores (GRSs) for elevated fasting glucose and insulin, reduced insulin secretion and sensitivity, and T2D, using variants discovered in studies of nonpregnant individuals. We tested for associations between these GRSs, glycemic traits in pregnancy, and GDM. In both cohorts, the fasting glucose GRS was strongly associated with fasting glucose. The insulin secretion and sensitivity GRSs were also significantly associated with these traits in Gen3G, where insulin measurements were available. The fasting insulin GRS was weakly associated with fasting insulin (Gen3G) or C-peptide (HAPO). In HAPO (207 GDM case subjects), all five GRSs (T2D, fasting glucose, fasting insulin, insulin secretion, and insulin sensitivity) were significantly associated with GDM. In Gen3G (43 GDM case subjects), both the T2D and insulin secretion GRSs were associated with GDM; effect sizes for the other GRSs were similar to those in HAPO. Thus, despite the profound changes in glycemic physiology during pregnancy, genetic determinants of fasting glucose, fasting insulin, insulin secretion, and insulin sensitivity discovered outside of pregnancy influence GDM risk.
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影响因子：
7.7
作者：
Kwak SH;Kim SH;Cho YM;Go MJ;Cho YS;Choi SH;Moon MK;Jung HS;Shin HD;Kang HM;Cho NH;Lee IK;Kim SY;Han BG;Jang HC;Park KS
通讯作者：
Park KS
影响因子：
5.8
作者：
Lauenborg, Jeannet;Grarup, Niels;Hansen, Torben
通讯作者：
Hansen, Torben
影响因子：
16.2
作者：
Stumvoll, M;Mitrakou, A;Gerich, J
通讯作者：
Gerich, J
新的遗传基因座涉及禁食葡萄糖稳态及其对2型糖尿病风险的影响。
影响因子：
30.8
作者：
通讯作者：
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影响因子：
16.2
作者：
Radaelli T;Farrell KA;Huston-Presley L;Amini SB;Kirwan JP;McIntyre HD;Catalano PM
通讯作者：
Catalano PM