Genetic Variations of TNF-α Gene and Their Associations with Type 2 Diabetes Mellitus and Serum Tnf-α Level in Thai

Presentation Number: SAT 600
Date of Presentation: April 1st, 2017

Sivaporn Wannaiampikul*1 and Somlak Chuengsamarn2
1Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand, 2Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, HRH Princess Maha Chakri Sirindhorn Medical Center, Srinakharinwirot University,, Nakornnayok, Thailand

Abstract

Genetic Variations of TNF-α Gene and their Associations with Type 2 Diabetes Mellitus and Serum TNF-α Level in Thai

Sivaporn Wannaimpikul1, Siwanon Jirawatnotai2, Vipavee Anupunpisit3, Somlak Chuengsamarn4

1Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok Thailand;

2Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;

3Department of Anatomy, Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand;

4Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, HRH Princess Maha Chakri Sirindhorn Medical Center, Srinakharinwirot University, Nakornnayok, Thailand .

Tumor Necrosis Factor-alpha (TNF-α) has been implicated in the pathogenesis of type 2 diabetes (DM) with metabolic syndrome related to insulin resistance. The correlation between TNF promoter genotypes and type 2 DM related to metabolic components is still controversial, because discrepancies among different studies exist. Ethnic differences play certain roles in these conflicting results, because the distribution of TNF tumor necrosis factor alpha promoter polymorphisms is different among study subjects with different racial origins. Therefore, we aim to clarify the association of two SNPs (rs1800629 and rs361525) located on the promoter of TNF-α gene with DM related to metabolic components in Thai patients. These two SNPs (rs1800629G>A and rs361525G>A) were detected in the case-control study, which composed of diabetes patients (n=433) and non-diabetes patients (n=348) by Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP). We found that only rs1800629 variants associated with increasing risk of being DM(adjusted OR=2.11, 95% CI=1.18-3.77, p=0.01). The rs1800629 variants carriers had higher values of fasting plasma glucose (FPG). In addition to the analysis of TNF-α level revealed that the presence of the rs1800629 variants was associated with decreased serum TNF-α level comparing to wild type carriers (p=0.035). There were no significant associations between rs361525 variations. Moreover, the haplotype analysis showed that the GA haplotype pattern (rs1800629 and rs361525) was significantly associated with increased risk to develop DM related to metabolic components (OR=1.84, 95% CI=1.06-3.18, p=0.03). Our study confirmed that rs1800629 variant was associated with DM related to metabolic components and might contribute to repress circulating TNF-α level in serum but not rs361525 in Thai population.

Nothing to Disclose: SW, SJ, VA, SC

 

Sources of Research Support: The National Research of Council Thailand (NRCT) grant to

SC (principal investigator)

Nothing to Disclose:S. Wannaiampikul, S. Jirawatnotai, V. Anupunpisit, and

S. Chuengsamarn, MD.

 

Nothing to Disclose: SW, SC