Abstract
BackgroundSeveral studies have shown that common variants in the MTNR1B gene were associated with fasting glucose level and type 2 diabetes. The purpose of this study was to examine whether tagging single nucleotide polymorphisms (SNPs) in the MTNR1B region were associated with type 2 diabetes and related traits in a Han Chinese population.MethodsWe investigated the association of polymorphisms in the MTNR1B gene with type 2 diabetes by employing a case-control study design (1118 cases and 1161 controls). Three tagging SNPs (rs10830963, rs3781637, and rs1562444) with R2>0.8 and minor allele frequency>0.05 across the region of the MTNR1B gene were studied. Genotyping was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy using a MassARRAY platform.ResultsThe polymorphism rs3781637 was associated with type 2 diabetes adjusted for age, sex and body mass index (BMI) in the additive model and recessive model (OR = 1.22, 95% CI 1.01-1.46, p = 0.038 and OR = 2.81, 95% CI 1.28-6.17, p = 0.01, respectively). In the non-diabetic controls, rs3781637 was nominally associated with plasma triglyceride, total cholesterol and low density lipoprotein cholesterol (LDL-C) levels in the recessive model (p = 0.018, 0.008 and 0.038, respectively). After adjustment for multiple comparisons, the associations of rs3781637 with total cholesterol and LDL-C remained significant in the recessive model (the empirical p = 0.024 and 0.045, respectively), but the association between rs3781637 and triglyceride became non-significant (the empirical p = 0.095). The associations of rs10830963 and rs1562444 with type 2 diabetes and related traits were not significant in the additive, dominant and recessive models.ConclusionsThe rs3781637 A/G polymorphism of the MTNR1B gene is associated with type 2 diabetes, plasma, total cholesterol and LDL-C levels in the Han Chinese population.
Highlights
Several studies have shown that common variants in the MTNR1B gene were associated with fasting glucose level and type 2 diabetes
Several large-scale genome-wide association analyses demonstrated that common variants in or near the MTNR1B gene to be robustly associated with fasting glucose level in European populations [6,7,8], with polymorphism rs10830963 showing the most significant association signal [7]
Associations of MTNR1B polymorphisms with quantitative traits in non-diabetic controls In the non-diabetic controls, the polymorphism rs3781637 was nominally associated with plasma triglyceride, total cholesterol and low density lipoprotein cholesterol (LDL-C) levels adjusted for age, sex and body mass index (BMI) in the recessive model (p = 0.018, 0.008 and 0.038, respectively) (Table 4, Figure 1)
Summary
Several studies have shown that common variants in the MTNR1B gene were associated with fasting glucose level and type 2 diabetes. Several replication studies in European [9,10,11,12], Indian [13], Sri Lankan and Japanese populations [14] confirmed that MTNR1B rs10830963 contributed to raised fasting glucose level and increased risk of type 2 diabetes. Ling et al first replicated the association of MTNR1B rs10830963 with type 2 diabetes and fasting glucose in a case-control study including 1165 type 2 diabetes cases and 1105 normoglycaemic controls [17]. Whether other common variants except rs10830963 in the MTNR1B gene are associated with type 2 diabetes and fasting glucose in Han Chinese population is unknown
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