The MTMR9 rs2293855 polymorphism is associated with glucose tolerance,insulin secretion,insulin sensitivity and increased risk of prediabetes |
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Authors: | L. Tang,Y. Tong,H. Cao,S. Xie,Q. Yang,F. Zhang,Q. Zhu,L. Huang,Q. Lü ,Y. Yang,D. Li,M. Chen,C. Yu,W. Jin,Y. Yuan,N. Tong |
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Affiliation: | 1. Division of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, Sichuan, China;2. Division of Endocrinology and Metabolism, Chengdu Fifth People''s Hospital, Chengdu, Sichuan, China;3. Chengdu Aerospace Hospital, Chengdu, Sichuan, China;4. Department of Clinical Medicine, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China;5. Chengdu Yincao Community Hospital, Chengdu, Sichuan, China |
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Abstract: | BackgroundPolymorphism of rs2293855 in gene MTMR9 has been associated with obesity and metabolic syndrome. We aim to study the association of rs2293855 with type 2 diabetes mellitus (T2DM) intermediate phenotypes in a Han Chinese population.MethodsThe polymorphism was genotyped in 838 Han Chinese individuals using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS); all participants underwent a 75 g oral glucose tolerance test (OGTT); associations between the polymorphism and glucose tolerance, indices of insulin secretion and indices of insulin sensitivity were analyzed.ResultsThe frequency of genotypes and alleles differed significantly between normal glucose tolerance and prediabetes (P = 0.043 and P = 0.009, respectively). The GG homozygous presented higher fasting plasma glucose (P = 0.009), higher 2-hour plasma glucose (P = 0.024) and higher glucose area under the curve (AUC, P = 0.01). Moreover, the G allele of rs2293855 was associated with glucose intolerance (fasting glucose, P = 0.012; glucose AUC, P = 0.006; 2-h glucose, P = 0.024); it is also associated with decreased indices of insulin sensitivity (fasting insulin, P = 0.043; insulin sensitivity index composite, P = 0.009; homeostasis model assessment of insulin resistance, HOMA-IR, P = 0.008) and decreased indices of insulin secretion (HOMA of beta cell function, HOMA-B, P = 0.028; insulinogenic index, P = 0.003). In addition, the minor allele G was also associated with increased risk of prediabetes (OR = 1.463, 95%CI: 1.066–2.009, P = 0.018).ConclusionsPolymorphism of rs2293855 in MTMR9 is associated with measures of glucose tolerance, indices of insulin secretion and indices of insulin sensitivity. We also suggest that allele G is likely to increase the risk of prediabetes by influencing both insulin secretion and insulin sensitivity. |
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Keywords: | MTMR9, myotubularin related protein 9 gene SNP, single nucleotide polymorphism NGT, normal glucose tolerance T2DM, type 2 diabetes mellitus BMI, body mass index WC, waist circumference Matsuda ISI, Matsuda insulin sensitivity index HOMA-IR, homeostasis model assessments of insulin resistance HOMA-B, homeostasis model assessments of β-cell function OGTT, oral glucose tolerance test HbA1c, glycated hemoglobin MALDI-TOF MS, Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry ANOVA, analysis of variance OR, odds ratio CI, confidence interval AUC, area under the curve IGT, impaired glucose tolerance GWAS, genome-wide association studies MAGIC, Meta-Analyses of Glucose and Insulin-related traits Consortium IFG, impaired fasting glucose ins(1,3)P2, inositol 1,3-bisphosphate |
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