循环网膜素-1 水平而非遗传变异影响 2 型糖尿病的病理生理学。

Circulatory Omentin-1 levels but not genetic variants influence the pathophysiology of Type 2 diabetes.

机构信息

Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara 390002, Gujarat, India.

Asian Bariatrics Hospital, Ahmedabad 380015, Gujarat, India.

出版信息

Cytokine. 2019 Jul;119:144-151. doi: 10.1016/j.cyto.2019.03.011. Epub 2019 Mar 23.

DOI:10.1016/j.cyto.2019.03.011

PMID:30909150

Abstract

OBJECTIVE

Omentin-1, an anti-inflammatory protein, is secreted by the visceral adipose tissue. Altered levels of Omentin-1 are associated with obesity and Type 2 Diabetes (T2D). Although Omentin-1 is implicated in the insulin signaling pathway, the relationship between the genetic variants of Omentin-1 and T2D is not yet explored. The current study evaluates the association of Omentin-1 polymorphisms (rs2274907 A/T and rs1333062 G/T), its transcript and protein levels, and genotype-phenotype correlation with metabolic parameters and T2D susceptibility.

METHODS

Plasma and Peripheral Blood Mononuclear Cells (PBMCs) were separated from venous blood taken from 250 controls and 250 T2D patients recruited from Gujarat, India. Genomic DNA was isolated from PBMCs and genotyping of Omentin-1 variants was performed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). RNA was isolated from Visceral Adipose Tissue (VAT) samples of 12 controls and 10 patients, and transcript levels of Omentin-1 were assessed by qPCR. Plasma Omentin-1 levels were estimated by ELISA. Fasting Blood Glucose, Body Mass Index (BMI) and plasma lipid profile were considered for the genotype-phenotype correlation analysis.

RESULTS

Our study revealed no association of Omentin-1 genetic variants with T2D risk (p > 0.05). However, the AT genotype of Omentin-1 rs2274907 A/T polymorphism was associated with increased BMI (p = 0.0247). Plasma Omentin-1 levels were significantly decreased (p < 0.0001) however, increased VAT Omentin-1 transcript levels (p = 0.0127) were observed in T2D patients.

CONCLUSION

Our findings suggest that decreased circulatory Omentin-1 levels could pose a risk towards T2D susceptibility.

摘要

目的

内脂素 -1 是一种具有抗炎作用的蛋白，由内脏脂肪组织分泌。内脂素 -1 水平的改变与肥胖和 2 型糖尿病（T2D）有关。虽然内脂素 -1 与胰岛素信号通路有关，但内脂素 -1 基因变异与 T2D 之间的关系尚未得到探索。本研究评估了内脂素 -1 多态性（rs2274907A/T 和 rs1333062G/T）、其转录本和蛋白水平，以及基因型-表型相关性与代谢参数和 T2D 易感性的关系。

方法

从印度古吉拉特邦招募的 250 名对照者和 250 名 T2D 患者的静脉血中分离血浆和外周血单核细胞（PBMCs）。从 PBMCs 中提取基因组 DNA，并通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对 Omentin-1 变体进行基因分型。从 12 名对照者和 10 名患者的内脏脂肪组织（VAT）样本中分离 RNA，并通过 qPCR 评估 Omentin-1 的转录水平。通过 ELISA 测定血浆内脂素 -1 水平。考虑基因型-表型相关性分析的空腹血糖、体重指数（BMI）和血浆脂质谱。

结果

本研究未发现 Omentin-1 遗传变异与 T2D 风险相关（p>0.05）。然而，Omentin-1 rs2274907A/T 多态性的 AT 基因型与 BMI 增加相关（p=0.0247）。然而，T2D 患者的血浆内脂素 -1 水平显著降低（p<0.0001），而 VAT 内脂素 -1 转录水平升高（p=0.0127）。