IL12RB2 Gene Is Associated with the Age of Type 1 Diabetes Onset in Croatian Family Trios

Abstract

BackgroundCommon complex diseases are influenced by both genetic and environmental factors. Many genetic factors overlap between various autoimmune diseases. The aim of the present study is to determine whether four genetic variants known to be risk variants for several autoimmune diseases could be associated with an increased susceptibility to type 1 diabetes mellitus.Methods and FindingsWe genotyped four genetic variants (rs2358817, rs1049550, rs6679356, rs9865818) within VTCN1, ANXA11, IL12RB2 and LPP genes respectively, in 265 T1DM family trios in Croatian population. We did not detect association of these polymorphisms with T1DM. However, quantitative transmission disequilibrium test (QTDT, orthogonal model) revealed a significant association between the age of onset of T1DM and IL12RB2 rs6679356 variant. An earlier onset of T1DM was associated with the rs6679356 minor dominant allele C (p = 0.005). The association remained significant even after the Bonferroni correction for multiple testing and permutation.ConclusionsVariants originally associated with juvenile idiopathic arthritis (VTCN1 gene), sarcoidosis (ANXA11 gene), primary biliary cirrhosis (IL12RB2 gene) and celiac disease (LPP gene) were not associated with type 1 diabetes in our dataset. Nevertheless, association of IL12RB2 rs6679356 polymorphism with the age of T1DM onset suggests that this gene plays a role in defining the time of disease onset.

A study of 51 subtypes of peripheral blood immune cells in newly diagnosed young type 1 diabetes patients

“…4d,e). These findings, along with other similar studies [38][39][40][41], suggest the presence of a more prominent proinflammatory profile of immune cells in children with a younger age at onset of T1D than those diagnosed at older ages. In addition, our previous study suggests that the timing by which immunological markers are investigated following the onset of T1D is critical in understanding disease development [42].…”

“…However, older children had higher values of slan -CD16 -mDC and non-activated (HLA-DR -CD38 -) CD4 + and CD8 + T cells compared to younger children (Fig. These findings, along with other similar studies [38][39][40][41], suggest the presence of a more prominent proinflammatory profile of immune cells in children with a younger age at onset of T1D than those diagnosed at older ages. 4d,e).…”

Association of PTPN22 gene polymorphism with type 1 diabetes mellitus in Chinese children and adolescents

“…The prevalence of T1DM accounts for 5-10% of all diabetes cases (Gale, 2002;Awoniyi et al, 2013;Lipman et al, 2013). Although the exact pathogenesis of T1DM is unknown, T1DM is thought to involve multifactor disorders resulting from genetic polymorphisms as well as various environmental factors (Rich et al, 2006;Ei Wafai et al, 2011;Pehlić et al, 2012;Hadžija et al, 2013). Previous studies have indicated that genetic polymorphisms in genes such as TRAIL (Bernardi et al, 2012), HLA (Black and Dabelea, 2013), and CCR5 (Yang et al, 2004) were associated with T1DM risk.…”

Exceptional manifestation of polyautoimmunity in a very young girl – a case report

“…The co-occurrence of juvenile idiopathic arthritis and type 1 diabetes mellitus is known and has been previously described [ 4 , 6 – 9 ]. In our patient, symptoms of type 1 diabetes mellitus occurred after the recognition of juvenile idiopathic arthritis.…”

“…Numerous genetic studies have demonstrated more than fifty susceptibility genes, which indicate the possibility of co-occurrence of autoimmune diseases including connective tissue diseases and the digestive system diseases with celiac disease [ 9 ].…”