Relationship between exon 3 (+/-) genotypes of growth hormone receptor and metabolic risk factors in patients in pre-diabetic state

Background: Metabolic impacts of two important alleles of the growth hormone receptors (GHR), one with retention of exon 3 exon 3 (+) GHR and the other with the deletion of it exon 3 (-) GHR, on the metabolic risk factors of type 2 diabetes mellitus (T2DM) are really unknown. We aimed to evaluate relationships between the genotypes and metabolic risk factors of T2DM. Methods: In the present study, 40 patients in pre-diabetic state and 40 healthy subjects were selected based on their clinical and laboratory evidence. For genotyping, DNA was extracted from the leukocytes of peripheral blood and amplified by multiplex polymerase chain reaction method. Genotypes of the amplified DNA samples were resolved using 1.5% agarose gel electrophoresis. Other risk factors were also determined by using standard methods and appropriate kits. Findings: Frequency of the homozygote exon 3 retained genotype exon 3 (+/+) GHR was significantly higher in the subject in pre-diabetic state (P < 0.001); the frequency of exon 3 (+/-) GHR and exon 3 (-/-) GHR genotypes were significantly higher in the control subjects (P < 0.001). The decrease of metabolic risk factors was profound in subjects with exon 3(-/-) GHR genotype (P < 0.001). Conclusion: The presence of exon 3 deleted allele of GHR, especially in the homozygosity situation, was associated with decreased levels of the metabolic risk factors of type 2 diabetes mellitus. So, the exon 3 deleted GHR may have more robust biological and metabolic activities lead to the resistance against T2DM