Ren Jie, Xiang Anny H, Trigo Enrique, Takayanagi Miwa, Beale Elizabeth, Lawrence Jean M, Hartiala Jaana, Richey Joyce M, Allayee Hooman, Buchanan Thomas A, Watanabe Richard M
Department of Preventive Medicine, Keck School of Medicine of USC, 2250 Alcazar St, Los Angeles, CA, 90089-9073, USA.
Diabetologia. 2014 Jul;57(7):1391-9. doi: 10.1007/s00125-014-3239-3. Epub 2014 Apr 13.
AIMS/HYPOTHESIS: MTNR1B is a type 2 diabetes susceptibility locus associated with cross-sectional measures of insulin secretion. We hypothesised that variation in MTNR1B contributes to the absolute level of a diabetes-related trait, temporal rate of change in that trait, or both.
We tested rs10830963 for association with cross-sectional diabetes-related traits in up to 1,383 individuals or with rate of change in the same phenotypes over a 3-5 year follow-up in up to 374 individuals from the family-based BetaGene study of Mexican Americans.
rs10830963 was associated cross-sectionally with fasting glucose (p = 0.0069), acute insulin response (AIR; p = 0.0013), disposition index (p = 0.00078), glucose effectiveness (p = 0.018) and gestational diabetes mellitus (OR 1.48; p = 0.012), but not with OGTT 30 min Δinsulin (the difference between the 30 min and fasting plasma insulin concentration) or 30 min insulin-based disposition index. rs10830963 was also associated with rate of change in fasting glucose (p = 0.043), OGTT 30 min Δinsulin (p = 0.01) and AIR (p = 0.037). There was no evidence for an association with the rate of change in beta cell compensation for insulin resistance.
CONCLUSIONS/INTERPRETATION: We conclude that variation in MTNR1B contributes to the absolute level of insulin secretion but not to differences in the temporal rate of change in insulin secretion. The observed association with the rate of change in insulin secretion reflects the natural physiological response to changes in underlying insulin sensitivity and is not a direct effect of the variant.
目的/假设：MTNR1B是一个与胰岛素分泌横断面指标相关的2型糖尿病易感基因座。我们推测MTNR1B的变异会导致糖尿病相关性状的绝对水平、该性状的时间变化率或两者都发生变化。
在基于家庭的墨西哥裔美国人BetaGene研究中，我们对rs10830963与多达1383名个体的横断面糖尿病相关性状，或与多达374名个体在3至5年随访期间相同表型的变化率进行了关联测试。
rs10830963与空腹血糖（p = 0.0069）、急性胰岛素反应（AIR；p = 0.0013）、处置指数（p = 0.00078）、葡萄糖效能（p = 0.018）和妊娠期糖尿病（OR 1.48；p = 0.012）呈横断面关联，但与OGTT 30分钟胰岛素变化量（30分钟和空腹血浆胰岛素浓度之间的差异）或基于30分钟胰岛素的处置指数无关。rs10830963还与空腹血糖变化率（p = 0.043）、OGTT 30分钟胰岛素变化量（p = 0.01）和AIR（p = 0.037）相关。没有证据表明与胰岛素抵抗的β细胞代偿变化率有关联。
结论/解读：我们得出结论，MTNR1B的变异会导致胰岛素分泌的绝对水平发生变化，但不会导致胰岛素分泌时间变化率的差异。观察到的与胰岛素分泌变化率的关联反映了对潜在胰岛素敏感性变化的自然生理反应，而不是该变异的直接作用。
