Atrial fibrillation (AF) occurrence has a known genetic component. Many reports have revealed a correlation between gene mutation and AF, involving genes related to ion channels, connexin (Cx), and those within the angiotensin system. In this study, the correlation between the Cx 40 polymorphism (rs35594137) and AF was investigated in patients with AF in the Xinjiang, Turpan, and Kashi regions and in controls. The AF cohort included 122 patients (58 Han and 64 Uygur). The control subjects were recruited according to the 1:1 corresponding method and matched for age and gender. Polymerase chain reaction-restriction enzyme fragment length polymorphism was used to analyze Cx 40 (rs35594137) genotype and allele distributions. Compared with the control group, A allele and A allele frequency were higher in the promoter region of Cx 40 (rs35594137) site (P < 0.05). In the Uygur population, the distribution of rs35594137 genotype and allele frequencies was not significantly different (P > 0.05) from the AF and control groups of Chinese Han origin. The confounding factors, including coronary heart disease, hypertension, smoking, and drinking, were evaluated by multivariate conditional logistic regression analysis. Cx 40 (rs35594137) differences between AF and control groups of Han origin were not significant (P > 0.05), but were statistically significant in the Uygur population (P < 0.05). These results demonstrated that Cx 40 (rs35594137) was associated with AF. In the Uygur population, Cx 40 (rs35594137) should be considered as an independent risk factor for patients with AF, who might have racial differences in rs35594137 variant frequencies.