A study to investigate genetic factors associated with weight gain in people with diabetes: analysis of polymorphisms in four relevant genes

Abstract

Background Weight change is often seen in people with diabetes. We investigated the effects of genes associated with weight change/glucose handling/insulin-signalling. Materials/methods DNA from diabetes individuals and non-diabetes individuals, plus clinical data, were available from the DARE study ( n = 379 individuals: T1D n = 111; T2D n = 222; controls n = 46). Weight gain was assessed by temporal change of Body Mass Index (BMI). Genotyping was performed for CAV1 rs926198, LEPR rs1137101, BDNF rs6265 and FTO rs9939609. Results No differences in genotype distributions were observed for the four SNPs in all groups un-stratified by weight gain. Following stratification differences in genotype distribution were observed. For those BMI relatively stable; controls showed a difference in genotype distributions versus T1D ( CAV1 rs926198, LEPR rs1137101). In T2D vs controls, significant differences were observed in genotype distribution for all four genes. For BMI increase, the only difference by category was LEPR rs1137101 (bothT1D/T2D vs controls). In BMI-stable groups, CAV1 rs926198, T1D individuals showed lower T allele frequency ( p =0.004) vs non-diabetes and for LEPR rs1137101 a higher G allele frequency versus controls ( p =0.002). For T2D, CAV1 rs926198, T allele frequency was lower in T2D than controls ( p =0.005). For LEPR rs1137101, the G allele frequency was higher than in controls ( p =0.004). In those with BMI increase, LEPR rs1137101 T1D individuals had higher G allele frequency versus controls ( p =0.002) as did T2D vs controls ( p =0.03). Conclusion Differences in allele frequency were seen between diabetes individuals and non-diabetes diagnosed at baseline in relation to the likelihood of BMI increase of >10%. It is established that the G allele of LEPR rs1137101 is associated with weight gain/obesity. However, this is the first report of CAV1 rs926198 polymorphism being associated with weight stability/gain in diabetes.