Groin hernias emerge at the myopectineal orifice of Fruchaud which is closed off by the fascia transversalis. Our previous studies showed structural and quantitative changes of the fascia transversalis elastic fibers of inguinal hernia patients and elderly people. The present study used single-strand conformation polymorphism (SSCP) elastin (analysis to investigate the 34 exons of the ELN gene of 49 inguinal hernia patients (7 females, 42 males aged 58.7 ± 19.82 years) and 75 non-herniated controls (35 females, 40 males aged 46.2 ± 14.32 years). We found that 47 patients and 24 controls had an abnormal exon 20 pattern caused by a g28197A > G missense mutation leading to an S422G amino acid substitution in the elastin hydrophobic domain. The g28197A > G allele frequency was 0.71 ± 0.045 in hernia patients and 0.21 ± 0.030 in controls and 23 patients and 7 controls were g28197A > G homozygous and 24 patients and 17 controls were heterozygous. This point-mutation showed a statistically significant association with inguinal hernia, chi-squared being 46.89 (p < 0.001) and the odds ratio 49.93 (95% confidence interval of @11 to 223). These results indicate that the g28197A > G mutation is involved in the genesis of inguinal hernia (possibly due to abnormal elastic fiber production) and explains impaired fascia transversalis function. Key words: fascia transversalis, extracellular matrix, elastic fibers, elastin gene, inguinal hernia. All groin hernias emerge at the myopectineal orifice of Fruchaud which is closed off by the fascia transversalis, a connective tissue composed of a framework of elastic and collagen fibers, which supports the abdominal tension forces.The elastic fibers are composed of microfibrils and elastin and are responsible for the resilience of the fascia transversalis. Research by our group has shown age-related structural changes (breaching and wrapping) in the elastic fibers, with ultrastructural studies showing a large decrease in the quantity of microfibril component ( Rodrigues Jr. et al., 1990;Quintas et al., 2000). Some studies have shown reduced amounts of collagen in the fascia transversalis of patients with direct inguinal hernia compared to those with indirect hernia, suggesting that the development of some hernias might be influenced by disturbances in collagen metabolism (Pans et al., 2001;Rodrigues Jr et al., 2002). Taken together, these results indicate that there is a loss of tensile resistance and elasticity in the fascia transversalis tissue which may explain the high incidence of inguinal hernia after the fifth decade of life.Mutations in the elastin (ELN) gene may be responsible for disorders of the elastic fiber system because they have been observed in cases of supravalvular aortic stenosis and autosomal dominant cutis laxa, individuals with either of these conditions may show smooth and soft skin, hernias, gastrointestinal diverticula and genital prolapse (Ewart et al., 1994;Li et al., 1997;Meng et al., 1998;Tassabehji et al., 1998). These reports and our previous st...