Association investigation of BACH2 rs3757247 and SOD2 rs4880 polymorphisms with the type 1 diabetes and diabetes long-term complications risk in the Polish population

Abstract

Abstract. Genetic factors are indicated in the development of type 1 diabetes (DM1). Recently, nucleotide variants of BACH2 and SOD2 have been associated with this chronic condition. Therefore, the purpose of the present study was to investigate the contribution of BACH2 rs3757247 and SOD2 rs4880 (Ala16Val) polymorphisms to the risk of DM1 and diabetes long-term complications. Selected polymorphic variants of BACH2 and SOD2 were investigated in a group of 141 patients with DM1 and in a group of age, gender-matched healthy subjects (n=369) using a high-resolution melting curve method. There was no evidence for either allelic or genotypic association with the risk of DM1 and diabetes chronic complications for analysed polymorphisms. In addition, no interaction between BACH2 and SOD2 variants in the development of this condition was observed. However, the frequency of BACH2 rs3757247 AG and AA genotypes was statistically different between DM1 patients with retinopathy and healthy individuals (odds ratio, 2.455; 95% confidence interval, 0.999-6.035; P=0.044), but this result did not survive multiple testing corrections. The present study did not confirm the involvement of BACH2 rs3757247 and SOD2 rs4880 polymorphisms in the development of DM1 and diabetes long-term complications. Further studies in a larger population sample are required. IntroductionType 1 diabetes (DM1) is a multifactorial disease that results from autoimmune destruction of β-cells in the pancreas (1). DM1 characterises the largest range of concordance rates in monozygotic twins among all autoimmune diseases, and this provides convincing evidence that genetic factors are strongly involved in the pathogenesis of DM1 (2). Initially, based on family-based linkage analyses, the strong association between human leukocyte antigen (HLA) class II genes encoding cell-surface antigen-presenting proteins and DM1 was found (3). With the advent of high-throughput single-nucleotide polymorphism (SNP) genotyping array technology studies, searching for the novel DM1 loci became possible (4). Based on the results of these studies, >60 new loci were identified across the human genome, which were associated with the risk of DM1 (5). In addition, advanced genetic technologies have become an important strategy to identify genetic factors contributing to the development of chronic diabetic complications (6,7).Recently, follow-up analysis of a genome-wide association study was performed on DM1 patients and revealed that an SNP in the intron of the BTB and CNC homology 1, basic leucine zipper transcription factor 1 (BACH2) gene (rs3757247) was associated with the risk of DM1 (8).The protein product of BACH2 plays a role as a key regulator of nucleic acid-triggered antiviral responses in human cells (9). It has been shown that Bach2 is expressed in the early stages of B-cell differentiation and is suppressed in terminally differentiated plasma cells by repressing the expression of B lymphocyte-induced maturation protein-1, the key regulator

The rs11755527 polymorphism in the BACH2 gene and type 1 diabetes mellitus: case control study in a Brazilian population

“…Wegner and cols. (28) investigated the rs3757247 SNP of the BACH2 gene in T1DM patients from Poland and did not find any significant association between the analyzed SNP and T1DM. In addition to the association with T1DM, other GWAS studies combined with meta-analyses have indicated that BACH2 SNPs are associated with other autoimmune diseases such as asthma (29), Cohn's diseases (30), coeliac disease (31), vitiligo (32), and Grave's disease (33).…”

Polymorphic variations and mRNA expression of the genes encoding interleukins as well as enzymes of oxidative and nitrative stresses as a potential risk of nephrolithiasis development

“…As mentioned above, inflammation may develop as a result of the formation of a deposit, or it may be a consequence of the intensification of oxidative stress processes observed in the course of urolithiasis [ 64 ]. Therefore, in our study we also analysed polymorphism located in SOD2 , encoding superoxide dismutase 2.…”

Variation of genes encoding nitric oxide synthases and antioxidant enzymes as potential risks of multiple sclerosis development: a preliminary study

“…The increased activity of this enzyme leads to an enhancement in the level of H 2 O 2 , which is then removed by CAT. Therefore, numerous polymorphisms, that occur within this gene [especially c.47C > T— SOD2 (rs4880)], play an essential role in the development mechanism of various diseases, including cancers (breast, prostate, bladder, and cervical cancers), depression, coronary artery disease, and type 1 diabetes 35 , 44 – 48 . According to data provided by NCBI dbSNP, 39,247 SNPs in this gene have been registered.…”