BACKGROUND: Factors governing adipose tissue differentiation play a major role in obesity development in humans. The Kr?l-like zinc finger transcription factor KLF2/Lung KLF (LKLF) is a negative regulator of adipocyte differentiation. In this study, we sequenced the human KLF2 gene and several common polymorphisms were found, among them the Pro104Leu and 3'UTR 1239C>A polymorphisms. METHODS: To evaluate the impact of these polymorphisms on anthropometric variables in humans, we genotyped a general population composed of 1155 French individuals (including 232 obese subjects) for these polymorphisms and looked for potential statistical associations with obesity-related variables. RESULTS: The frequency of the Leu104 and 1239A alleles were 0.22 and 0.18 respectively. Genotype and allele frequencies of the two polymorphisms were comparable in obese, overweight and normal weight subjects. No association between the rare alleles of the polymorphisms and anthropometric variables (BMI, weight, waist and hip circumferences, waist-to-hip ratio and plasma leptin levels) could be detected. Haplotype analyses did not reveal further significant associations. CONCLUSION: These data indicate that the Pro104Leu and 3'UTR 1239C>A polymorphisms in KLF2 are not associated with obesity and obesity-related traits in humans.