Role of the KCNJ Gene Variants in the Clinical Outcome of Type 1 Diabetes

Abstract

Diabetes is considered as a disease with a wide and continuous clinical spectrum, ranging from Type 1 (T1D) and Type 2 Diabetes (T2D) with complex multifactorial causes. In the last years, particular attention has been focused on the predictive value and therapeutic potential of single nucleotide polymorphisms (SNPs). SNPs can alter the seed-sequence in miRNA’s loci and miRNA target sites causing changes in the structure and influencing the binding function. Only few studies have investigated the clinical influence of SNPs, in particular potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ) gene variants in T1D population. The aim of the study is to investigate the occurrence and the possible metabolic significance of KCNJ polymorphism in a group of pediatric patients with T1D. The study was performed in a cohort of 90 Caucasian children and adolescents with T1D and 93 healthy subjects. Rs5210 polymorphism has been analyzed with a prevalence of the GG genotype in the patient group suggesting its association with T1D. Therefore, a relationship was found between GG genotype and body mass index (BMI) at diagnosis and insulin requirement (IR) after 6 months. The study suggested an action for rs5210 in determining the metabolic features of T1D pediatric patients, by showing some clues of insulin resistance in patients carrying that polymorphism.

Role of HNFA1 Gene Variants in Pancreatic Beta Cells Function and Glycaemic Control in Young Individuals with Type 1 Diabetes

“…In contrast to previous studies reporting an association of MODY genes and T1D susceptibility [13][14][15], in the present work, we did not find significant differences by comparing HNF1A SNPs frequencies between HC and T1D individuals.…”

“…To date, there are numerous genes known to be involved in the predisposition to the development of T1D [12], but no effect of the HNFA1 gene is known. Moreover, very few studies have already reported a possible role in T1D of other genes involved in the development of rarest forms of MODY, namely NeuroD1 (MODY6), ABCC8 (MODY12), and KNCJ11(MODY13) genes [13][14][15]. In addition to T1D susceptibility, Blasetti et al [15] also found an association between rs5210 SNP in the KCNJ11 gene and clinical features of T1D, such as BMI at onset and insulin requirement.…”

“…Moreover, very few studies have already reported a possible role in T1D of other genes involved in the development of rarest forms of MODY, namely NeuroD1 (MODY6), ABCC8 (MODY12), and KNCJ11(MODY13) genes [13][14][15]. In addition to T1D susceptibility, Blasetti et al [15] also found an association between rs5210 SNP in the KCNJ11 gene and clinical features of T1D, such as BMI at onset and insulin requirement. The authors also observed higher C-peptide at onset, suggesting a degree of insulin resistance in rs5210 carrier and speculating on the similarity between T1D and T2D.…”