Mastitis is a major cause of economic loss in dairy cattle. In this study, the bovine CACNA2D1 gene was taken as a candidate gene for mastitis resistance. The objective of this study was to identify single nucleotide polymorphisms (SNPs) in the bovine CACNA2D1 gene and evaluate the association of these SNPs with mastitis in cattle. Through DNA sequencing and PCR-RFLP analysis, three mutations C367400T, A496561G and G519663A were detected in the cattle CACNA2D1 gene. Altogether 240 dairy cattle of three breeds (Holstein, Simmental, and Sanhe cattle) were genotyped and allele frequencies were determined. The effects of CACNA2D1 polymorphisms on somatic cell score (SCS) were analyzed and a significant association was found between G519663A and SCS. The mean of genotype GG was significantly lower than those of genotypes AG and AA. The results of this research will be useful in further studies to determine the role of the CACNA2D1 gene in mastitis resistance and further work will be necessary to investigate whether the CACNA2D1 gene play a role in defending the host from mastitis.Key words: Association analysis, CACNA2D1 gene, dairy breeds, mastitis, somatic cell score