Abstract: AIM:To analyze the correlation of polymorphisms of KLOTHO gene G-395A and heart failure and myocardial fibrosis in middle-aged and elderly patients. METHODS: Two hundred and twelve non-sanguineously related middle-aged and elderly patients were randomly selected and peripheral blood leucocyte genome DNA was extracted. KLOTHO gene G-395-A polymorphic loci were detected using the single allele-specific primer PCR technique and the statistical significance of the distribution in different age groups was analyzed. At the same time, the blood concentrations of serum I carboxy-terminal peptide of procollagen (PICP) and III procollagen amino-terminal peptide (PIIINP) were detected using ELISA. The correlation of KLOTHO gene G-395A polymorphisms with heart failure and myocardial fibrosis was analyzed. RESULTS: G-395-A polymorphism loci presented three genotypes. No significant difference was seen in the site of genotype frequency distribution in middle-aged and elderly patients (χ2=12.159 P=0.121). Further analysis between any two age groups and genotype frequency distribution found no significant difference. KLOTHO gene G-395-A polymorphism was significantly associated with heart disease risks in middle-aged and elderly patients (χ2 = 23.634 P=0.00). AG was found 1.991 times more susceptible to heart failure than GG and AA was 1.527 times more susceptible to heart failure than GG. GG might be a protective factor for heart failure. No statistical difference was found between heart failure classifications and myocardial fibrosis degrees (P=0.202). No significant difference was found in the concentrations of collagen type I and III and in I/III concentration ratios compared with the three genotypes of G-395-A in middle-aged and elderly patients and were not related to genotypes. CONCLUSION: In middle-aged and elderly patients, KLOTHO gene promoter region G-395-A presents three types of polymorphism and the three polymorphisms are all significantly associated with the onset of heart failure. The risk of heart failure in patients with A alleles is significantly higher than that in patients with G allele and GG may be a protective factor for heart failure. The difference between the classifications of heart failure and the degrees of myocardial fibrosis are not statistically significant.