Genetic variation of SORBS1 gene is associated with glucose homeostasis and age at onset of diabetes: A SAPPHIRe Cohort Study

Abstract

The SORBS1 gene plays an important role in insulin signaling. We aimed to examine whether common single-nucleotide polymorphisms (SNPs) of SORBS1 are associated with prevalence and incidence of diabetes, age at onset of diabetes, and the related traits of glucose homeostasis. A total of 1135 siblings from 492 ethnic Chinese families were recruited at baseline, and 630 were followed up for 5.19 ± 0.96 years. Nine SNPs including rs7081076, rs2281939, rs3818540, rs2274490, rs61739184, rs726176, rs2296966, rs17849148, and rs3193970 were genotyped and examined. To deal with correlated data of subjects within the same families, the generalized estimating equations approach was applied throughout all association analyses. The GG genotype of rs2281939 was associated with a higher risk of diabetes at baseline, an earlier onset of diabetes, and higher steady-state plasma glucose levels in the modified insulin suppression test. The minor allele T of rs2296966 was associated with higher prevalence and incidence of diabetes, an earlier onset of diabetes, and higher 2-h glucose during oral glucose tolerance test. These two SNPs revealed independent associations with age of diabetes onset as well as risk of diabetes at baseline. These findings supported that SORBS1 gene participates in the pathogenesis of diabetes.

Early‐onset type 2 diabetes is associated with genetic variants of β‐cell function in the Chinese Han population

“…The conventional clinical risk factors lack specificity between EOD and LOD . In recent decades, various genetic variants have been found to be associated with the risk of EOD and/or onset age . In present study, the risk alleles of CDKN2BAS and ZFAND6 , both of which play an essential role in insulin secretion, were nominally associated with an earlier onset age.…”

“…Conventional clinical risk factors, including ethnicity, family history, intrauterine exposure to hyperglycemia, low birth weight, puberty, previous gestational diabetes, obesity, low physical activity, sedentary behavior, socioeconomic status, and others have been shown to contribute to EOD, but most of these factors also contribute to LOD, resulting in a lack of specificity . It has long been speculated that EOD patients could have a strong genetic predisposition to the disease, and several genetic variants were previously demonstrated to be associated with onset age among type 2 diabetes patients …”

Quantitative Proteomic and Network Analysis of Differentially Expressed Proteins in PBMC of Friedreich’s Ataxia (FRDA) Patients

“…SORBS1 plays an important function in the signaling and stimulation of insulin-stimulated glucose transport. Involvement of SORBS1 has also been reported recently in diabetic nephropathy (Chang et al, 2018). Release of SORBS1 from damaged cardiac tissue into the bloodstream was observed in patients with acute myocardial infarction (Kakimoto et al, 2013).…”

Transcriptomic Responses of Skeletal Muscle to Acute Exercise in Diabetic Goto-Kakizaki Rats

“…Cbl-associated protein (CAP), encoding by Sorbs1 , played a positive role in the insulin signaling pathway (Baumann et al, 2000). The genetic variation of Sorbs1 was associated with the incidence of diabetes and glucose homeostasis, supporting the involvement of Sorbs1 in the pathogenesis of diabetes (Chang et al, 2018). Besides, the expression of Sorbs1 was correlated negatively with homeostatic model assessment for insulin resistance (HOMA-IR).…”