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MTMR9基因的rs2293855多态性与葡萄糖耐量、胰岛素分泌、胰岛素敏感性以及糖尿病前期风险增加相关。

The MTMR9 rs2293855 polymorphism is associated with glucose tolerance, insulin secretion, insulin sensitivity and increased risk of prediabetes.

作者信息

Tang L, Tong Y, Cao H, Xie S, Yang Q, Zhang F, Zhu Q, Huang L, Lü Q, Yang Y, Li D, Chen M, Yu C, Jin W, Yuan Y, Tong N

机构信息

Division of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, Sichuan, China.

Department of Clinical Medicine, West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.

出版信息

Gene. 2014 Aug 10;546(2):150-5. doi: 10.1016/j.gene.2014.06.028. Epub 2014 Jun 14.

Abstract

BACKGROUND

Polymorphism 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.

METHODS

The 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.

RESULTS

The 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).

CONCLUSIONS

Polymorphism 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.

摘要

背景

MTMR9基因中rs2293855的多态性与肥胖和代谢综合征相关。我们旨在研究汉族人群中rs2293855与2型糖尿病(T2DM)中间表型的关联。

方法

采用基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF MS)对838名汉族个体的该多态性进行基因分型;所有参与者均接受75g口服葡萄糖耐量试验(OGTT);分析该多态性与葡萄糖耐量、胰岛素分泌指标及胰岛素敏感性指标之间的关联。

结果

正常糖耐量和糖尿病前期之间的基因型和等位基因频率存在显著差异(分别为P = 0.043和P = 0.009)。GG纯合子的空腹血糖较高(P = 0.009)、餐后2小时血糖较高(P = 0.024)且曲线下葡萄糖面积较高(AUC,P = 0.01)。此外,rs2293855的G等位基因与葡萄糖不耐受相关(空腹血糖,P = 0.012;葡萄糖AUC,P = 0.006;餐后2小时血糖,P = 0.024);它还与胰岛素敏感性指标降低相关(空腹胰岛素,P = 0.043;胰岛素敏感性指数综合指标,P = 0.009;胰岛素抵抗稳态模型评估,HOMA-IR,P = 0.008)以及胰岛素分泌指标降低相关(β细胞功能的HOMA,HOMA-B,P = 0.028;胰岛素生成指数,P = 0.003)。此外,次要等位基因G还与糖尿病前期风险增加相关(OR = 1.463,95%CI:1.066 - 2.009,P = 0.018)。

结论

MTMR9基因中rs2293855的多态性与葡萄糖耐量指标、胰岛素分泌指标及胰岛素敏感性指标相关。我们还表明,等位基因G可能通过影响胰岛素分泌和胰岛素敏感性增加糖尿病前期风险。

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