| Object:To investigate the frequencies of growth hormone receptor (GHR) exon 3 polymorphism in Chinese children with short stature and normal children, to study the differences between two groups in molecular level by comparing genotype distribution of GHR gene exon 3 deletion polymorphism and to study the relationship between GHR exon 3 polymorphism and the effect of recombinant human growth hormone (rhGH) therapy.Materials and Methods:In our study, we selected 143 children with short stature(including 58 growth hormone deficiency and 85 non-growth hormone deficiency) as study group and 170 healthy children with normal stature as control group. Genomic DNA was extracted from their leukocytes. A simple multiplex polymerase chain reactions (PCR) technique was used to detect the GHR gene exon 3 deletion polymorphism. Then we choose 70 children with short stature (including 45 growth hormone deficiency and 25 idiopathic short stature) who were treated with rhGH more than 3 months from study group. A mean rhGH dose of 0.1IU/Kg-d or 0.15IU/Kg-d was administered in these patients every night. No other steroids drugs were used during rhGH therapy. The data was analysed by SPSS16.0 (t test, Pearson correlation analysis and X2 test).Results:1.The frequencies of GHR exon 3 fl/fl, fl/d3 or d3/d3 were 49.7%,40.6%及9.8%, the allele frequency of f1,d3 was 69.9%,30.1% in study group; The frequencies of GHR exon 3 f1/f1, f1/d3 or d3/d3 were 64.1%,28.8%及6.5%, the allele frequency of f1,d3 was 79.1%,20.9%in control group. The proportion of f1/d3,d3/d3 and d3 in study group was obviously higher than control group. There was significant difference between two groups (P<0.05).2.There was significant difference between the two groups (fl/fl vs fl/d3 or d3/d3) in growth velocity of 45 growth hormone deficiency (GHD) and 25 idiopathic short stature (ISS) patients(P>0.05).3. In the patients whose GH stimulation test peak were<5ng/ml, there was significant difference in GV(9.11±1.47 vs 12.31±3.11) between the two groups (f1/f1 vs f1/d3 or d3/d3) (P<0.05). However, in those whose GH peaks between 5 and lOng/ml, there was no significant difference in GV(9.55±2.76 vs 10.84±1.53) between the two groups (fl/fl vs fl/d3 or d3/d3) (P>0.05), the results were different from those in the group of GH peak<5ng/ml patients. There was also no significant difference in GV in the GHD patients with same genotypes but different GH stimulation test peaks (P>0.05).4. In male GHD patients, there were no significant differences in GV(10.19±2.07 vs 11.22±1.69) between the two groups(fl/fl vs fl/d3 or d3/d3) (P>0.05); in female GHD patients, there were significant difference in GV (7.86±2.05 vs 12.13±3.67) between the two groups (fl/fl vs fl/d3 or d3/d3) (P<0.05), the results were different from those in male patients. There were no significant differences in GV(11.22±1.69 vs 12.13±3.67) between the two groups (male vs female) in GHD patients whose genotype was fl/d3 or d3/d3 (P>0.05); but there were significant difference in GV(10.19±2.07 vs 7.86±2.05) between the two groups (male vs female) in GHD patients whose genotype was fl/fl (P<0.05).5. The P values of Pearson analysis in GV vs GH peak was less than0.05.6. There were no significant differences in FT3,FT4,TSH'GLU of 20 children with short stature between before and after treatment (P>0.05), but there were no significant differences in GV of 20 children with short stature between before and after treatment (P<0.05).Conclusions:Differences in genotype distribution of GHR gene exon 3 deletion polymorphism exist in children with short stature and children with normal stature. The allele frequencies of GHR exon 3 of Chinese GHD patients are different from those of foreign GHD patients which suggest that the GHR exon 3 may have a racial variation. There is some relationship between GHR exon 3 polymorphism, GH peak and the effect of rhGH therapy. Exon 3-deleted genotype of growth hormone receptor (GHRd3) is associated with increased responsiveness to GH in GHD patients whose GH peaks were less than 5. The GV is correlated with GH peak. |
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