Diabetes-associated HLA genotypes affect birthweight in the general population

Area of Science:

• Immunogenetics
• Perinatal Epidemiology
• Human Genetics

Background:

• Type 1 diabetes (T1D) is an autoimmune disease with complex genetic and environmental factors.
• Birthweight is a known risk factor for T1D, but the underlying mechanisms are not fully understood.
• Human Leukocyte Antigen (HLA) genes are critical for immune regulation and are strongly associated with T1D susceptibility.

Purpose of the Study:

• To investigate the association between HLA genotypes, cord blood autoantibodies, and birthweight in newborns.
• To test the hypothesis that HLA genotypes conferring T1D risk are associated with increased birthweight.

Main Methods:

• Analysis of HLA genotypes from cord blood of 16,709 newborns in the Diabetes Prediction in Skåne (DiPiS) study.
• Exclusion of infants born to mothers with diabetes or gestational diabetes.
• Measurement of autoantibodies to glutamic acid decarboxylase (GAD65Ab) and insulinoma-associated protein 2.
• Classification of birthweight into high relative birthweight (HrBW) and low relative birthweight (LrBW) quartiles.

Main Results:

• HLA genotypes associated with T1D risk showed a significant association with relative birthweight (p=0.01).
• High-risk HLA genotypes (e.g., HLA-DQ2/8) were linked to HrBW (OR=1.20, p=0.0006).
• GAD65Ab were negatively associated with HrBW (OR=0.72, p=0.01), and HLA associations with birthweight were independent of confounders.

Conclusions:

• HLA genotypes may influence intrauterine growth independently of their role in T1D risk.
• The association between high birthweight and T1D risk might be moderated by HLA genotypes influencing fetal growth.