Alternative titles; symbols
Cytogenetic location: 2p21 Genomic coordinates (GRCh38): 2:41,500,001-47,500,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 2p21 | [Leptin serum levels QTL1] | 601694 | 2 |
Leptin (LEP; 164160) is a serum protein produced by adipocytes and is thought to play a role in the regulation of body fat. Leptin levels in humans are highly correlated with the individual's total adiposity (Maffei et al., 1995; Considine et al., 1996).
Comuzzie et al. (1997) performed a genomewide scan and conducted multipoint linkage analysis using a general pedigree-based variance component approach to identify genes with measurable effects on quantitative variation in leptin levels in Mexican Americans. Strong evidence of linkage between serum leptin level and a microsatellite polymorphism, D2S1788, was found; lod score = 4.95. The D2S1788 marker mapped to chromosome 2p21, approximately 74 cM from the tip of the short arm. This quantitative trait locus accounted for 47% of the variation in serum leptin level, with a residual additive genetic component contributing an additional 24%. Comuzzie et al. (1997) noted that this region contains several potential candidate genes for obesity, including glucokinase regulatory protein (GCKR; 600842) and proopiomelanocortin (POMC; 176830). The region may contain an important human obesity gene. Rotimi et al. (1999) confirmed the QTL on chromosome 2 for serum leptin levels.
Hixson et al. (1999) typed additional markers in the region of the LSL locus, increasing the lod score to 7.46. Because this region of chromosome 2 contained the strong positional candidate gene POMC, Hixson et al. (1999) used polymorphisms in POMC to map the locus within the 95% confidence interval of the peak for the linkage signal for the QTL. Hixson et al. (1999) also constructed POMC haplotypes using these polymorphisms and found a significant association with normal variation in leptin levels (P of 0.001). They concluded 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.
Comuzzie, A. G., Hixson, J. E., Almasy, L., Mitchell, B. D., Mahaney, M. C., Dyer, T. D., Stern, M. P., MacCluer, J. W., Blangero, J. A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2. Nature Genet. 15: 273-276, 1997. [PubMed: 9054940] [Full Text: https://doi.org/10.1038/ng0397-273]
Considine, R. V., Sinha, M. K., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Nyce, M. R., Ohannesian, J. P., Marco, C. C., McKee, L. J., Bauer, T. L., Caru, J. F. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. New Eng. J. Med. 334: 292-295, 1996. [PubMed: 8532024] [Full Text: https://doi.org/10.1056/NEJM199602013340503]
Hixson, J. E., Almasy, L., Cole, S., Birnbaum, S., Mitchell, B. D., Mahaney, M. C., Stern, M. P., MacCluer, J. W., Blangero, J., Comuzzie, A. G. Normal variation in leptin levels is associated with polymorphisms in the proopiomelanocortin gene, POMC. J. Clin. Endocr. Metab. 84: 3187-3191, 1999. [PubMed: 10487685] [Full Text: https://doi.org/10.1210/jcem.84.9.5951]
Maffei, M., Halaas, J., Ravussin, E., Pratley, R. E., Lee, G. H., Zhang, Y., Fei, H., Kim, S., Lallone, R., Ranganathan, S., Kern, P. A., Friedman, J. M. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nature Med. 1: 1155-1161, 1995. [PubMed: 7584987] [Full Text: https://doi.org/10.1038/nm1195-1155]
Rotimi, C. N., Comuzzie, A. G., Lowe, W. L., Luke, A., Blangero, J., Cooper, R. S. The quantitative trait locus on chromosome 2 for serum leptin levels is confirmed in African-Americans. Diabetes 48: 643-644, 1999. [PubMed: 10078570] [Full Text: https://doi.org/10.2337/diabetes.48.3.643]