The C allele of c.-94C>G polymorphism of the delta-sarcoglycan gene was associated as a risk factor for coronary spasm in Japanese patients with hypertrophic cardiomyopathy (HCM). We evaluated whether the c.-94C>G polymorphism can be a risk factor for HCM in Mexican patients. The polymorphism was genotyped and the risk was estimated in 35 HCM patients and 145 healthy unrelated individuals. Data of this polymorphism reported in Mexican Amerindian populations were included. The C allele frequency in HCM patients was higher with an odds ratio (OR) of 2.37, and the risk for the CC genotype increased to 5.0. The analysis with Mexican Amerindian populations showed that the C allele frequency was significantly higher in HCM patients with an OR of 2.96 and for CC genotype the risk increased to 7.60. The C allele of the c.-94C>G polymorphism is a risk factor for HCM, which is increased by the Amerindian component and can play an important role in the etiology and progression of disease in Mexican patients.