Does the relative risk for type 1 diabetes conferred by HLA-DQ, INS, and PTPN22 polymorphisms vary with maternal age, birth weight, or cesarean section?

Background and objective: Maternal age at birth, birth weight, and cesarean section has been associated with a weak but significant increase in risk of type 1 diabetes. The objective was to assess whether the relative risk for type 1 diabetes conferred by established susceptibility loci human leukocyte antigen (HLA)-DQ, INS, and PTPN22 differed depending on these perinatal factors. Methods: We employed a case-control study with 456 cases of type 1 diabetes diagnosed before 15 yr of age and 1377 population-based control children. HLA genotypes were divided into high to moderate risk (DQ8/DQ2, DQ8/DQ8, DQ8/X, DQ2/DQ2) vs. all other genotypes. Case-only analysis using logistic regression was used to test for significant interaction. Results: There was no significant difference in the relative risks conferred by HLA-DQ, INS, or PTPN22 by maternal age, birth weight, or mode of delivery, except the relative risk conferred by PTPN22 which was 2.11 [95% confidence interval (CI): 1.64-2.72] for those born vaginally and 0.99 (95% CI: 0.50-1.99) for those born by cesarean section [p(interaction) = 0.028]. Conclusion: The relative risks conferred by the three established susceptibility genes investigated here were independent of the perinatal factors, apart from a possible interaction between PTPN22 and mode of delivery.