Analysis of the d3-growth hormone receptor polymorphism in large cohorts of small, appropriate and large for gestational age newborns.

Background: Several studies evidenced a possible role of the d3-Growth Hormone Receptor (GHR) polymorphism in fetal growth. The GHR genotype distribution was studied in small (SGA) and appropriate (AGA) for gestational age newborns but never in the large (LGA) for gestational age babies. The aim of this study was to evaluate the frequencies of this polymorphism in a large cohort of SGA, AGA and LGA newborns.

Methods: A total of 536 healthy newborns, randomly selected among the infants referred to the Italian North-Eastern centre for endocrinological and metabolic newborn screening, were enrolled: 192 SGA, 200 LGA and 144 AGA. Weight was recorded at birth. Isoforms of d3-GHR gene (fl/fl, d3/fl, and d3/d3) were analysed.

Results: The analysis of the GHR genotype evidenced a lower frequency of the d3/d3 genotype in SGA cohort compared to the AGA population (P=0.005), or to the total population (P=0.035). No differences were found in the genotypic distribution between LGA and AGA population (P=0.373), or between LGA and the whole population (P=0.292).

Conclusions: d3/d3 GHR genotype was found twice as frequent in AGA and LGA cohorts compared to SGA subjects, whereas no significant differences in the frequency distribution of the GHR genotypes between LGA and AGA newborns were detected. The data leads to the exclusion of the GHR exon 3 deletion polymorphism as a possible genetic factor leading to LGA pregnancies.