Association between non-coding polymorphisms of HOPX gene and syncope in hypertrophic cardiomyopathy

OBJECTIVE: Homeodomain Only Protein X (HOPX) is an unusual homeodomain protein which regulates Serum Response Factor (SRF) dependent gene expression. Due to the regulatory role of HOPX on SRF activity and the regulatory role of SRF on cardiac hypertrophy, we aimed to investigate the relationship between HOPX gene variations and hypertrophic cardiomyopathy (HCM). METHODS: In this study, designed as a case-control study, we analyzed coding and flanking non-coding regions of the HOPX gene through 67 patients with HCM and 31 healty subjects. Certain regions of the gene were investigated by Single Stranded Conformation Polymorphism (SSCP) and Restriction Fragment Length Polymorphism (RFLP). Statistical analyses of genotypes and their relationship with clinical parameters were performed by chi-square, Kruskal-Wallis and the Fisher's exact test. RESULTS: In 5' Untranslated Region (UTR) and intronic region of the HOPX gene, we found a C>T substitution and an 8-bp insertion/deletion (In/Del) polymorphism, respectively. These two polymorphisms seemed to constitute an haplotype. While the frequency of homozygous genotypes of In/Del and C/T polymorphisms were found significantly lower in the patients with syncope (p=0.014 and p=0.017, respectively), frequency of their heterozygous genotypes were found significantly higher in the patients with syncope (p=0.048 and p=0.030, respectively). CONCLUSİON: Though there was not found any mutation in coding sequence of HOPX gene, two non-coding polymorphisms were found related to syncope in HCM patients. While homozygous status of these polymorphisms was found to be protective against the syncope, their heterozygous status seemed to be a risk factor for syncope in HCM patients. Our results suggest that HOPX may contribute to pathogenesis or manifestation of HCM as a modifier gene.