Association of the growth hormone receptor gene polymorphisms with mandibular height in a Korean population

Growth hormone receptor gene (GHR) is one of the likely candidates for determining morphological traits, because GH is a key regulator of bone growth. The genetic association of GHR in exon 10 with mandibular ramus height has been found in different populations, Japanese and Chinese. On the other hand, two common isoforms of GHR, one full-length (fl-GHR) and the other lacking the extracellular domain encoded by exon 3 (d3-GHR), are associated with differences in responsiveness to GH. The purpose of this study involving 159 Korean subjects was to study the associations between a GHR polymorphism (d3/fl-GHR) that results in genomic deletion of exon 3 and craniofacial morphology, and to study the associations between GHR genotypes in exon 10 and craniofacial morphology. Moreover, the allelic frequencies in a multi-ethnic population (24 Han Chinese, 24 African-Americans, 24 European-Americans, and 24 Hispanics) in a GHR polymorphism (d3/fl-GHR) were compared in this study. The five craniofacial linear measurements (cranial base length, maxillary length, overall mandibular length, mandibular corpus length, and mandibular ramus height) obtained from lateral cephalograms were examined as craniofacial morphology. We found that the d3/fl-GHR polymorphism had no association for any measurements, and a statistically significant association (P = 0.024) between the GHR polymorphisms P561T and C422F in exon 10 and mandibular ramus height. Neither SNPs besides P561T and C422F polymorphisms in exon 10 nor the measurements besides mandibular ramus height have statistically significances. Both derived alleles at P561T and C422F SNPs were highly associated with only one haplotype, haplotype-4 in Korean population. As quantitative haplotype association, the results showed a significant difference in mandibular ramus height between individuals having one haplotype-4 and others without haplotype-4 (P = 0.028). Moreover, we found that the d3/fl-GHR polymorphism showed diverse frequency in different population. Regarding GHR genotypes in exon 10, the present study mostly reflected the results obtained for a Japanese population, although our current study does not replicate the correlation between the I526L polymorphism of GHR and mandibular ramus height as was reported in a previous study of Han Chinese. The results of the present study suggest that the GHR exon 10 SNPs, not d3/fl-GHR, contribute to changes in the mandibular ramus height of Koreans.