Associations of common variants in the SLC16A11, TCF7L2, and ABCA1 genes with pediatric-onset type 2 diabetes and related glycemic traits in families: A case-control and case-parent trio study

Background: There is evidence of associations of single-nucleotide polymorphisms (SNPs) with type 2 diabetes (T2D) and related glycemic traits in adults, but there is a little information about such associations in youths.

Objective: The aim of this study was to evaluate the associations of SNPs in the TCF7L2, SLC16A11, and ABCA1 genes with T2D and related glycemic traits in Mexican children and adolescents.

Subjects: A total of 99 families with children with T2D (n = 327) and 83 families with children without the disease (n = 212).

Methods: The associations between SNPs of TCF7L2 (rs7903146 and rs12255372), SLC16A11 (rs13342232), and ABCA1 (rs9282541) with T2D were analyzed. We also evaluated the effects of SNPs on quantitatively related glycemic traits after adjusting for age, sex, and the presence of overweight or obesity.

Results: The G allele of SLC16A1 /rs13342232 was associated with T2D in adults (adjusted odds ratio [ORadj] = 1.89; 95% confidence interval [CI]: 1.18; 3.06) and children (ORadj = 1.94; 95% CI: 1.25; 3.00). In addition, the combined analysis of case-control and case-parent trio was also significant (OR = 1.43; 95% CI: 1.12; 1.74). After adjusting for known confounding factors, we found a significant association between TCF7L2/rs122555372 and C-peptide (β = -0.76, P = .005) in patients with diabetes and between fasting glucose (β = 2.05, P = .039) and homeostatic model assessment of β-cell function (β = -32.14, P = .025) levels in individuals without diabetes.

Conclusions: The results suggest that SLC16A1 /rs13342232 might be involved in the risk of pediatric-onset T2D in Mexican families. Moreover, TCF7L2/rs122555372 was associated with pancreatic reserve in patients with T2D and with fasting glucose and β-cell function in individuals without diabetes.