Department of Pediatrics, Section of Genetics, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Nutr Metab Cardiovasc Dis. 2012 Nov;22(11):944-51. doi: 10.1016/j.numecd.2011.01.006. Epub 2011 May 10.
Two common variants (rs1387153, rs10830963) in MTNR1B have been reported to have independent effects on fasting blood glucose (FBG) levels with increased risk to type 2 diabetes (T2D) in recent genome-wide association studies (GWAS). In this investigation, we report the association of these two variants, and an additional variant (rs1374645) within the GWAS locus of MTNR1B with FBG, 2h glucose, insulin resistance (HOMA IR), β-cell function (HOMA B), and T2D in our sample of Asian Sikhs from India. Our cohort comprised 2222 subjects [1201 T2D, 1021 controls]. None of these SNPs was associated with T2D in this cohort. Our data also could not confirm association of rs1387153 and rs10830963 with FBG phenotype. However, upon stratifying data according to body mass index (BMI) (low ≤ 25 kg/m(2) and high > 25 kg/m(2)) in normoglycemic subjects (n = 1021), the rs1374645 revealed a strong association with low FBG levels in low BMI group (β = -0.073, p = 0.002, Bonferroni p = 0.01) compared to the high BMI group (β = 0.015, p = 0.50). We also detected a strong evidence of interaction between rs1374645 and BMI with respect to FBG levels (p = 0.002). Our data provide new information about the significant impact of another MTNR1B variant on FBG levels that appears to be modulated by BMI. Future confirmation on independent datasets and functional studies will be required to define the role of this variant in fasting glucose variation.
两种常见的 MTNR1B 变异体（rs1387153，rs10830963）在最近的全基因组关联研究（GWAS）中被报道对空腹血糖（FBG）水平具有独立影响，增加了 2 型糖尿病（T2D）的风险。在这项研究中，我们报告了这两个变体以及 MTNR1B 的 GWAS 位点内的另一个变体（rs1374645）与 FBG、2h 血糖、胰岛素抵抗（HOMA IR）、β细胞功能（HOMA B）和我们来自印度的亚洲锡克教样本中的 T2D 的关联。我们的队列包括 2222 名受试者[1201 名 T2D，1021 名对照]。在这个队列中，这些 SNP 都与 T2D 无关。我们的数据也不能证实 rs1387153 和 rs10830963 与 FBG 表型的关联。然而，在根据正常血糖受试者（n = 1021）的体重指数（BMI）（低≤25kg/m（2）和高>25kg/m（2））对数据进行分层后，rs1374645 与低 BMI 组的低 FBG 水平有很强的关联（β=-0.073，p=0.002，Bonferroni p=0.01），而与高 BMI 组的关联较弱（β=0.015，p=0.50）。我们还检测到 rs1374645 与 BMI 对 FBG 水平的相互作用有很强的证据（p=0.002）。我们的数据提供了关于另一种 MTNR1B 变体对 FBG 水平的显著影响的新信息，这种影响似乎受 BMI 调节。需要在独立数据集和功能研究中进行进一步确认，以确定该变体在空腹血糖变化中的作用。
