Lack of Association Between HPGD and SMAD3 Gene Nucleotide Changes and Digital Clubbing Cases With Cancer

Objectives: HPGD encoding an enzyme that plays an important role on regulation of prostaglandin metabolism is the only gene underlines autosomal recessive isolated congenital nail clubbing. SMAD3 gene is a member of Smad family, are possibly tumor suppressor genes because alterations of these genes occurred in various carcinomas. The aim of this study was examined HPGD and SMAD3 mutations in seven-generation family with digital clubbing and cancer. Methods: The study group consisted of a seven-generation family with clinical features of digital clubbing and different types of cancer, and healthy controls. The family members and control group were evaluated for HPDG and SMAD3 gene mutations by DNA sequencing method. The present study also focused on biochemical characterization of SMAD3 single nucleotide polymorphisms in the family. Results: DNA sequencing analysis of the HPGD gene identified no functional sequence variant causing disease-phenotype in the family. But in this study, a novel single nucleotide polymorphism c. 1278G>A and three previously described polymorphisms IVS2+59C>G, c.309A>G, c.508A>G were identified in SMAD3 gene. Only A/G transition in codon 170 was found significant but this polymorphism was segregated with the affected and unaffected members of the family. Biochemical examination did not show statistically significant correlation between SMAD3 polymorphisms and digital clubbing. Conclusion: These findings suggest that the HPGD and SMAD3 genes may not play an important role in the pathogenesis of unexplained digital clubbing and cancer in this family.