Polymorphism and Allele Frequency Variation in Proximal End of Promoter and Exon 1 of Human Growth Hormone Gene in Pakistan- A Pilot Study

Growth hormone gene belongs to a highly polymorphic gene family whose members contain regions of very similar conserved sequences making this gene a challenging candidate to analyze. Almost 90% of the sequence of growth hormone gene family members is similar and prone to single nucleotide variations. The sequence variation occurring in the non-coding region of the GH-1 gene leads to altered transcriptional regulation causing various developmental defects in humans. In this report, we have analyzed a short sequence of ~200-240 bp spanning the proximal promoter and exon 1 (proximal portion) of the GH-1 gene to analyze the SNPs and allele frequencies of respective SNPs. Genomic DNA from blood was extracted, and the selected region was amplified using PCR. Sequencing of the amplified product was performed using Sanger sequencing, and the resulting sequence was analyzed. We have recorded 11 SNPs in total that occur in the VDRE region, 5’ UTR and untranslated region of exon 1. A greater number of the SNPs were observed to coincide with the reported data from various sources. Two SNPs at position -62 and -56 (relative to transcription start site) are novel and not reported elsewhere up to the best of our knowledge. The minor allele frequencies of SNPs at position -57, -50, -48, -40, -34, -1 and +58, respectively are higher than other populations. All the observed SNPs are located in the region involved in transcription factor binding. This study is the first report regarding the allele frequency data and SNPs of the GH promoter region and exon 1 in the Local population.