The combined physiological effects of somatotropic and gonadal axes have been demonstrated to cause acceleration in linear growth at puberty. In synergy, growth hormone (GH) and gonadal steroids (testosterone [T] and estradiol [E2]) stimulate longitudinal bone growth through direct stimulation of chondrocytes and osteoblasts. Amongst others, the secretion of GH is stimulated by ghrelin through its receptor called GH secretagogue receptor 1a (GHSR1a). Ghrelin is a peptide secreted by gastrointestinal mucosa of the digestive system. Ghrelin/GHSR1a system plays important roles in multiple physiological processes, especially in GH secretion and appetite regulation. The GHSR1a locus is one of the top sites suggested to contribute to the genetic variation of height. Therefore, the present study was designed to determine the association between GHSR1a variants and short stature in Pakistani population. Three SNPs, C173R, R273W and P108L in GHSR1a gene, were examined. Blood samples were obtained from 35 short stature patients (21 boys and 14 girls) exhibiting short stature and decreased appetite and 30 normal healthy controls. DNA was extracted, primers of exons of GHSR1a splice sites were designed and PCR-RFLP method was employed. The PCR product of GHSR1a digested by enzyme PstI for C173R mutation gave bands of two different genotypes, normal TT (381 and 155 bp) in 14 short stature boys and 7 short stature girls and heterozygous TC (536, 381 and 155 bp) in 7 short stature boys and 7 short stature girls. All the controls gave normal TT genotype for C173R SNP. Furthermore, the PCR product of GHSR1a digested by enzyme PvuII for R273W mutation gave bands of two different genotypes, normal AA (144 and 32 bp) in 12 short stature boys and 9 short stature girls and heterozygous AT (176, 144 and 32 bp) in 9 short stature boys and 5 short stature girls. All the controls gave normal AA genotype for R273W SNP. On the other hand, the PCR product of GHSR1a digested by enzyme HeaIII for P108L mutation gave bands of CC (155 and 24 bp). The frequency of this genotype was 100% in controls and short stature children indicating absence of P108L mutation in both groups. In conclusion, C173R and R273W SNPs of GHSR1a gene might be associated with short stature in Pakistani population.
22 May 2021 - 26 May 2021