Abstract: AIM To study the relationship between KCNE1 polymorphism-G38S and chronic heart failure in the Chinese Uygur in Xinjiang. METHODS PCR-restriction fragment length polymorphism (PCR-RFLP) analysis was conducted to detect the genotype of G38S (rs1805127) of the KCNE1 gene in 200 chronic heart failure (CHF) patients and 200 non-CHF subjects (control). RESULTS Polymorphism G38S AA, AG, GG genotype frequencies of KCNE1 were 24 cases (12.0%), 89(44.5%) and 87(43.5%) in CHF group and 37(18.5%), 91(45.5%) and 72(36.0%) in the control group, respectively. A and G allele frequencies were 137(34.2%) and 263 (65.8%) in the CHF group and 165 (41.2%) and 235 (58.8%) in the control group. There were no significant differences between the genotype frequencies of the two groups (χ²=4.208, P=0.122); however, the allele frequency of the two groups was statistically significant (χ²=4.170, P=0.041). Binary classification logistic regression analysis showed that the OR value of left ventricular end-diastolic diameter (LVEDD), QRS interval, gender, coronary heart disease (CHD), diabetes and AG genotype were 1.473 (95%CI:1.357-1.599), 1.028 (β=0.027, 95%CI:1.009-1.047), 2.288 (β=0.828, 95%CI:1.059-4.943), 3.047 (β=1.114, 95%CI:1.532-6.063), 3.200 (β=1.163, 95%CI:1.345-7.562) and 0.489 (β=-0.715, 95%CI:0.247-0.966), respectively. CONCLUSION G38S of KCNE1 in Uighur CHF patients carries higher G allele frequency than that in non-CHF patients. Increase of LVEDD, extension of QRS interval, male, CHD and diabetes are risk factors for CHF. An Uygur carrying the AG genotype has a lower risk of CHF. Therefore, the AG genotype may be a protective factor for CHF.