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To explore the association between the single nucleotide polymorphism (SNP) of leptin receptor (LEPR) gene and the susceptibility to osteoporosis (OP) among Chinese Mulao people. A total of 738 people were involved. Bone mineral density (BMD) was examined by calcaneus ultrasound attenuation measurement. Six SNPs of LEPR were detected. The genotypes, allele frequencies, linkage disequilibrium, and haplotype were analyzed. BMD decreased with age and males had higher BMD than women. The proportion of normal bone mass decreased with age, and morbidity of OP increased. Three out of six SNPs showed a difference between OP and normal group. Individuals with AA genotype of rs1137100 in OP group outnumber the normal group, AA increased the risk of OP. In rs2767485, CT increased the risk of OP, C allele may be susceptible to OP. TT genotype of rs465555 was susceptible genotype of OP, T locus may be associated with OP. Strong linkage disequilibrium was detected among rs1137100, rs1137101, and rs4655555. Four haplotypes were constructed, among which, AACGCT and GGTGTA increased the risk of OP by 3.9 and 4.2 times, respectively, whereas, GGCGTA reduced 74% of OP susceptibility. The rs1137100, rs2767485, and rs465555 of LEPR were associated with OP in Chinese Mulao people. [ABSTRACT FROM AUTHOR]