Polymorphisms of inflammatory genes as potential predictors of diabetic nephropathy in patients with type 2 diabetes [Polimorfizam upalnih gena kao mogući predskazatelj diabetičke nefropatije u bolesnika sa šećernom bolesti tipa 2]

Završnik, Matej (2019) Polymorphisms of inflammatory genes as potential predictors of diabetic nephropathy in patients with type 2 diabetes [Polimorfizam upalnih gena kao mogući predskazatelj diabetičke nefropatije u bolesnika sa šećernom bolesti tipa 2]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Objectives One of the more devastating chronic complications of diabetes mellitus (DM) is diabetic nephropathy (DN), with a chronic low-grade inflammation occurring in the background. The aim of this study is to examine the relationship between chosen candidate genes with potential functional importance in inflammation and DN among Caucasians with type 2 (T2DM) as markers to identify patients who are more likely to develop DN. ----- Methods and patients Participants were divided into two groups: patients with DN (276 subjects) and without DN (375 subjects). SNP genotyping for 13 SNPs from four fields of inflammation were performed: Adhesion molecules: ICAM1 gene (rs5498, rs1799969), PECAM1 (rs668); Chemokines: CCL5 (rs2280788, rs2107538), CCR5 (rs1799987) and the CCR2 (rs1799864); Interleukins (ILs): rs3212227, rs187238, rs1800896, rs2243250 of IL12B, IL18, IL10 and IL4 genes, respectively; Nuclear receptors: PPARG (rs1801282) and PPARGC1A (rs8192678). ----- Results No associations were found between the SNPs of chosen adhesion molecules (rs5498, rs1799969, rs668) and chemokines (rs2280788, rs2107538, rs1799987, rs1799864) and DN in T2DM patients. Similarly, no associations were found for SNPs from interleukins (rs3212227, rs187238, rs1800896, and rs2243250) and nuclear receptors (rs1801282, rs8192678) even with DN. Serum levels of sICAM-1, sPECAM-1, IL-18 and IL-10 did not differ between different genotypes of corresponding selected polymorphisms. ----- Conclusions Genetic polymorphisms from our set of genes involved in the inflammatory response were not found to be associated with DN in Caucasians with T2DM and may not be considered as potential markers for DN in this population. Additionally, no differences were found in serum levels of sICAM-1, sPECAM-1, IL-18 and IL-10 according to different genotypes of corresponding genes.

Abstract in Croatian

Cilj: Dijabetička nefropatija (DN), edna od težih kroničkih komplikacija šećerne bolesti (DM), posljedica je kronične upale niskog stupnja. Cilj istraživanja bio je utvrditi povezanost gena “kandidata” koji mogu biti važni za razvoj upale i DN u bijelaca s tipom 2 DM.(T2DM).Metode i bolesnici: Bolesnici su bili podijeljeni u skupine s DN (276 bolesnika) i bez DN (375 bolesnika). Obavljena je single nucleotide polymorphism (SNP) genotipizacija za 13 SNPs za četiri područja upale: adhezijske molekule: ICAM1 geni (rs5498, rs1799969), PECAM1 (rs668); kemokine: CCL5 (rs2280788, rs2107538), CCR5 (rs1799987) i CCR2 (rs1799864); interleukine (IL): rs3212227, rse87238, rs1800896, rs2243250 geni za IL12B, IL18, IL10 i IL4; nuklearne receptori: PPARG (rs1801282) i PPARGC1A (rs8192678). ----- Rezultati: Nije pronađena povezanost SNPs odabranih adhezijskih molekula (rs5498, rs1799969, rs668) i kemokina (rs2280788, rs2107538, rs1799987 i rs1799864) za DN u bolesnika s T2DM. Slično tome, nije pronađena povezanost sa SNP interleukina (rs3212227, rs187238, rs1800896 i rs2243250) i nuklearnih receptora (rs1801282, rs8192678) s DN. Razine sICAM-1, sPECAM-1, IL-18 i IL-10 u serumu nisu se razlikovale između različitih genotipova odgovarajućih odabranih polimorfizama. ----- Zaključci: Nije utvrđena povezanost za genski polimorfizmi naše odabrane skupine gena koji sudjeluju u upalnom odgovoru s DN u bijelaca s T2DM i zato se ne može smatrati mogućim biljezima za nastanak DN u toj populaciji. Također nisu utvrđene razlike u razini sICAM-1, sPECAM-1, IL-18 i IL-10 u serumu u različitim genotipovima odgovarajućih gena.

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