Normal variation in leptin levels in associated with polymorphisms in the proopiomelanocortin gene, POMC.
Normal variation in leptin levels in associated with polymorphisms in the proopiomelanocortin gene, POMC.
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DOI：
10.1210/jcem.84.9.5951
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发表时间：
1999-09
期刊：
影响因子：
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通讯作者：
J. Hixson;L. Almasy;Shelley A. Cole;S. Birnbaum;B. D. Mitchell;M. Mahaney;M. P. Stern;J. Maccluer;J. Blangero;A. Comuzzie
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文献类型：
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作者：
J. Hixson;L. Almasy;Shelley A. Cole;S. Birnbaum;B. D. Mitchell;M. Mahaney;M. P. Stern;J. Maccluer;J. Blangero;A. Comuzzie
我们之前报道过，我们的基因组扫描计划在墨西哥裔美国人家庭中检测到 2 号染色体上的数量性状基因座 (QTL) 与瘦素水平之间存在高度显着的关联（对数优势比 = 4.95；P = 9 x 10(-7)）。现在，我们在该区域输入了额外的微卫星标记，将对数优势比得分提高到 7.46 (P = 2 x 10(-9))。 2 号染色体的这个区域包含一个强位置候选基因 POMC。 POMC 基因编码 POMC，即产生 αMSH、ACTH 和 β-内啡肽的激素原。其他研究表明 POMC 衍生产品参与食欲和肥胖的调节。我们使用 POMC 中的多态性来绘制其在 QTL 连锁信号峰的 95% 置信区间内的位置。我们还利用这些多态性构建了 POMC 单倍型，并发现与瘦素水平的正常变化存在显着相关性 (P = 0.001)。我们得出结论，POMC 的变异与血清瘦素水平的正常变异相关，这进一步证明 POMC 可能是先前在墨西哥裔美国人家庭中发现的瘦素 QTL。
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.