Asociación de la variante GHRd3 del receptor de la hormona de crecimiento con autoinmunidad en la diabetes tipo 1

Abstract

Background: Growth Hormone Receptor (GRH) is expressed in the liver, pancreas, stomach and small intestine. A high expression of GHR mRNA in the mucosal gut suggests a possible role of this receptor on digestive and immune functions. Aim: To investigate the putative effects of the GHRd3 variants on the cytokine profile and distribution of auto-antibodies in children with type 1 diabetes (T1D). Material and Methods: Unrelated unaffected controls (n = 192) and incident cases of children with T1D (n = 127) were analyzed for GHRd3 polymorphism, cytokine profile and a panel of auto-antibodies. Results: The allele frequency for d3 was 24.8% in type 1 diabetics and 34.1% in controls (p = NS). Among type 1 diabetic children, the carriers of the GHRd3 polymorphism had significantly higher levels of interleukin-1ß than homozygous for the wild type genotype (5.7 and 17.7, pg/ml respectively, p<0.015). Carriers of d3 variant had a higher frequency of positive anti-insulin antibodies (anti-IAA) than children without this variant (39.6 and 17.7% respectively, p<0.01). Conclusions: The observed frequency of the GHR d3/d3 genotype was comparable to other reports. A relationshiop between d3 variant and anti-IAA antibodies and interleukin-1ß was observed.