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J Clin Endocrinol Metab. 1999 Sep;84(9):3187-91.

Normal variation in leptin levels in associated with polymorphisms in the proopiomelanocortin gene, POMC.

Author information

1
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas 78245, USA.

Abstract

We previously reported that our genome-scanning initiative had detected a highly significant linkage (log odds ratio = 4.95; P = 9 x 10(-7)) between a quantitative trait locus (QTL) on chromosome 2 and leptin levels in Mexican American families. We now have typed additional microsatellite markers in this region, increasing this log odds ratio score to 7.46 (P = 2 x 10(-9)). This region of chromosome 2 contains a strong positional candidate gene, POMC. The POMC gene codes for POMC, the prohormone from which alphaMSH, ACTH, and beta-endorphin are derived. Studies by others have shown that POMC-derived products are involved in the regulation of appetite and obesity. We have used polymorphisms in POMC to map its location within the 95% confidence interval of the peak for the linkage signal for the QTL. We also constructed POMC haplotypes using these polymorphisms and have found a significant association with normal variation in leptin levels (P = 0.001). We conclude that variation in POMC is associated with normal variation in serum leptin levels, providing further evidence that POMC may be the leptin QTL previously identified in Mexican American families.

PMID:
10487685
DOI:
10.1210/jcem.84.9.5951
[Indexed for MEDLINE]

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