Kawai Vivian K, Levinson Rebecca T, Adefurin Abiodun, Kurnik Daniel, Collier Sarah P, Conway Douglas, Stein Charles Michael
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Pharmacogenomics. 2017 Oct;18(15):1381-1386. doi: 10.2217/pgs-2017-0079. Epub 2017 Oct 4.
Sympathetic activation suppresses insulin secretion via pancreatic ADRA2A. Because sympathetic activity and insulin demand increase during pregnancy, we tested the hypothesis that ADRA2A variants are associated with gestational diabetes (GDM).
PATIENTS & METHODS: Among Caucasian pregnant women without pre-existing diabetes, we genotyped 458 who had GDM and 1537 without GDM for seven ADRA2A variants.
rs1800038 (OR: 2.34; p = 0.020) and rs3750625 (OR: 1.56; p = 0.010) increased the risk of GDM, and rs11195418 decreased it (OR: 0.62; p = 0.025). The associations remained significant after adjustment for maternal age, maternal BMI, parity and a genetic risk score that included variants previously associated with Type 2 diabetes mellitus and GDM.
ADRA2A genetic variation contributes independently to the risk of GDM in Caucasian women.
交感神经激活通过胰腺α2A肾上腺素能受体(ADRA2A)抑制胰岛素分泌。由于孕期交感神经活动和胰岛素需求增加,我们检验了ADRA2A基因变异与妊娠期糖尿病(GDM)相关的假说。
在无糖尿病病史的白种孕妇中,我们对458例患GDM的孕妇和1537例未患GDM的孕妇进行了7种ADRA2A基因变异的基因分型。
rs1800038(比值比:2.34;p = 0.020)和rs3750625(比值比:1.56;p = 0.010)增加了GDM风险,而rs11195418降低了GDM风险(比值比:0.62;p = 0.025)。在对产妇年龄、产妇体重指数、产次以及包含先前与2型糖尿病和GDM相关的变异的遗传风险评分进行校正后,这些关联仍然显著。
ADRA2A基因变异独立影响白种女性患GDM的风险。