Department of Life Science, Sogang University, Department of Obstetrics and Gynecology, Cheil General Hospital and Women’s Healthcare Center, 1 Shinsu-dong, Mapo-gu, Seoul, 121-742, Republic of Korea.
BMC Med Genet. 2011 Jun 10;12:82. doi: 10.1186/1471-2350-12-82.
Two SNPs in melatonin receptor 1B gene, rs10830963 and rs1387153 showed significant associations with fasting plasma glucose levels and the risk of Type 2 Diabetes Mellitus (T2DM) in previous studies. Since T2DM and gestational diabetes mellitus (GDM) share similar characteristics, we suspected that the two genetic polymorphisms in MTNR1B may be associated with GDM, and conducted association studies between the polymorphisms and the disease. Furthermore, we also examined genetic effects of the two polymorphisms with various diabetes-related phenotypes.
A total of 1,918 subjects (928 GDM patients and 990 controls) were used for the study. Two MTNR1B polymorphisms were genotyped using TaqMan assay. The allele distributions of SNPs were evaluated by x2 models calculating odds ratios (ORs), 95% confidence intervals (CIs), and corresponding P values. Multiple regressions were used for association analyses of GDM-related traits. Finally, conditional analyses were also performed.
We found significant associations between the two genetic variants and GDM, rs10830963, with a corrected P value of 0.0001, and rs1387153, with the corrected P value of 0.0008. In addition, we also found that the two SNPs were associated with various phenotypes such as homeostasis model assessment of beta-cell function and fasting glucose levels. Further conditional analyses results suggested that rs10830963 might be more likely functional in case/control analysis, although not clear in GDM-related phenotype analyses.
There have been studies that found associations between genetic variants of other genes and GDM, this is the first study that found significant associations between SNPs of MTNR1B and GDM. The genetic effects of two SNPs identified in this study would be helpful in understanding the insight of GDM and other diabetes-related disorders.
先前的研究表明，褪黑素受体 1B 基因中的两个单核苷酸多态性（SNP）rs10830963 和 rs1387153 与空腹血浆葡萄糖水平和 2 型糖尿病（T2DM）的发病风险显著相关。由于 T2DM 和妊娠期糖尿病（GDM）具有相似的特征，我们怀疑 MTNR1B 中的这两个遗传多态性可能与 GDM 相关，并进行了这两种多态性与疾病之间的关联研究。此外，我们还检查了这两种多态性与各种糖尿病相关表型的遗传效应。
共纳入 1918 例受试者（928 例 GDM 患者和 990 例对照）进行研究。采用 TaqMan 法检测 MTNR1B 上的两个 SNP。采用 x2 模型计算比值比（OR）、95%置信区间（CI）和相应的 P 值，评估 SNP 等位基因分布。采用多元回归分析进行 GDM 相关表型的关联分析。最后还进行了条件分析。
我们发现两个遗传变异与 GDM 显著相关，rs10830963 的校正 P 值为 0.0001，rs1387153 的校正 P 值为 0.0008。此外，我们还发现这两个 SNP 与各种表型如胰岛β细胞功能和空腹血糖水平的稳态模型评估有关。进一步的条件分析结果表明，尽管在 GDM 相关表型分析中并不明确，但 rs10830963 在病例/对照分析中可能更具功能。
先前有研究发现其他基因的遗传变异与 GDM 相关，这是首次发现 MTNR1B 的 SNP 与 GDM 显著相关的研究。本研究中鉴定的两个 SNP 的遗传效应将有助于理解 GDM 及其他糖尿病相关疾病的发病机制。
