IGF2 Gene Polymorphisms and IGF-II Concentration are Determinants of Longitudinal Weight Trends in Type 2 Diabetes

Abstract

Objective:

The hypothesis of the study was that IGF2 gene polymorphisms were associated with longitudinal trends in weight through modification of IGF-II concentration.

Design:

Observational study that explored associations of the IGF2 gene and baseline circulating IGF-II concentration with ‘real-world’ longitudinal trends in body-mass index in a type 2 diabetes population.

Methods:

26 haplotype tagging single nucleotide polymorphisms (SNPs) from the IGF2 and H19 genes were studied in 485 Caucasian individuals in the Salford Longitudinal Diabetes Cohort. A generalised-estimating equation (GEE) model was used to separately study the association of SNPs and IGF-II concentration with 8-year longitudinal trends in body-mass index.

Results:

High serum IGF-II concentration at baseline was associated with weight loss over the study period (β=−0.006, 95% CI −0.009 to −0.002, p<0.001). 8 SNPs were associated with longitudinal body-mass index trends, of which 4 retained significance after multiple ­testing correction. 2 SNPs rs10770063 and rs3842767 were associated with both IGF-II concentration as well as longitudinal weight changes.

Conclusion:

We report novel associations between polymorphisms in the IGF2 gene, with concentration of circulating IGF-II and also with longitudinal weight change in type 2 diabetes. Our data indicate that the IGF2 gene and its gene product may be important determinants of longitudinal weight trends in type 2 diabetes.

Key words

IGF-II - polymorphisms - body-mass index - real-world data - longitudinal associations - type 2 diabetes

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