Abstract
OBJECTIVE: We tested the hypothesis that polymorphisms in the cocaine- and amphetamine-regulated-transcript (CART) gene is associated with the development of obesity.
SUBJECTS: Five-hundred and twenty-eight subjects (325 men and 203 women) aged 49.6±11.0 y with body mass index (BMI) of 26.9±5.1.
MEASUREMENTS: The 5′-flanking region of the CART gene was cloned using adaptor-ligated genomic DNA fragments. The CART gene including the 5′-flanking region was screened for mutation by PCR-single strand conformation polymorphism and direct sequencing. Associations between polymorphisms and obesity were investigated by PCR-restriction fragment length polymorphism analysis and direct sequencing.
RESULTS: The 5′-flanking region of the CART gene up to −1072 bp from the transcription initiation site was sequenced. The region contained a putative cyclic AMP-responsive element and four E-box motifs upstream of a TATA box. Six polymorphic sites were identified in the upstream region; A→G at −156, T→C at −390, T→G at −484, G→T at −915, G→C at −929 and C→T at −962. The nucleotide substitution at −156 was significantly associated with greater BMI (P=0.036). The allele frequency of the −156 variant was significantly higher in obese subjects with BMI ≥30 than in non-obese subject (0.41 vs 0.32, P=0.0076). The −929 variant allele in linkage disequilibrium with the −156 variant was also more common in obese subjects. No mutation was found in the coding regions. A single nucleotide insertion/deletion polymorphism at +1355 in the 3′ untranslated region was not associated with obesity.
CONCLUSION: The 5′-flanking region of the CART gene was highly polymorphic. The −156 polymorphism or polymorphisms in linkage disequilibrium with the site may be associated with genetic predisposition to obesity.
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Yamada, K., Yuan, X., Otabe, S. et al. Sequencing of the putative promoter region of the cocaine- and amphetamine-regulated-transcript gene and identification of polymorphic sites associated with obesity. Int J Obes 26, 132–136 (2002). https://doi.org/10.1038/sj.ijo.0801848
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DOI: https://doi.org/10.1038/sj.ijo.0801848
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