Potential associations between variants of genes encoding regulators of inflammation, and mediators of inflammation in type 2 diabetes and insulin resistance


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Ozbayer C., Kebapci M. N., Kurt H., Colak E., Gunes H. V., Degirmenci I.

Journal of Clinical Pharmacy and Therapeutics, cilt.46, sa.5, ss.1395-1403, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 46 Sayı: 5
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1111/jcpt.13471
  • Dergi Adı: Journal of Clinical Pharmacy and Therapeutics
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, BIOSIS, CAB Abstracts, CINAHL, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.1395-1403
  • Anahtar Kelimeler: genetic variations, insulin Resistance, IRAK4, MyD88, TRAF6, type 2 diabetes, SIGNALING PATHWAY, IKK-BETA, KINASE 4, POLYMORPHISMS, MYD88, TLR4, CYCLOOXYGENASE-2, SUSCEPTIBILITY, CONSEQUENCES, NEPHROPATHY
  • Eskişehir Osmangazi Üniversitesi Adresli: Evet

Özet

What is known and objective: Type 2 diabetes (T2DM) is a multigenic disease that develops with impaired β-cell function and insulin sensitivity and has a high prevalence worldwide. A cause often postulated for type 2 diabetes is chronic inflammation. It has been suggested that inflammatory regulators can inhibit insulin signal transduction and that inflammation is involved in insulin resistance (IR) and the pathogenesis of type 2 diabetes. In this direction, we aimed to investigate the gene variants of MyD88 (rs1319438, rs199396), IRAK4 (rs1461567, rs4251513, rs4251559) and TRAF6 (rs331455, rs331457) and serum levels of COX-2, NF-κB, iNOS in T2DM and IR. Methods: The MyD88, IRAK4 and TRAF6 variations were genotyped in 100 newly diagnosed T2DM patients and 100 non-diabetic individuals using The MassARRAY® Iplex GOLD SNP genotyping method. The COX-2, iNOS and NF-κB levels were measured in serum samples with the sandwich-ELISA method. Results were analysed using SPSS Statistics software and the online FINNETI program. Results and discussion: In our study, a total of the 7 variants in the MyD88, IRAK4 and TRAF6 genes were genotyped, and as a result, no relationship was found between most of these variants and the risk of type 2 diabetes and insulin resistance (p > 0.05). Only, the rs1461567 variant of the IRAK4 gene was significant in the heterozygous model (CC vs. CT), and the CT genotype was most frequent in diabetic individuals compared with the non-diabetics (p = 0.033). Additionally, COX-2 and iNOS levels were found to be associated with diabetes and insulin resistance (p < 0.05). What is new and conclusion: Our results show that high COX-2 and iNOS levels are associated with T2DM, besides MyD88, IRAK4 and TRAF6 gene variations may not be closely related to type 2 diabetes and insulin resistance. Nevertheless, studies in this pathway with a different population and a large number of patients are important.