Evidence of a novel quantitative-trait locus for obesity on chromosome 4p in Mexican Americans
Evidence of a novel quantitative-trait locus for obesity on chromosome 4p in Mexican Americans
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DOI：
10.1086/381717
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发表时间：
2004-02-01
影响因子：
9.8
通讯作者：
Stern, MP
中科院分区：
文献类型：
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作者：
Arya, R;Duggirala, R;Stern, MP
尽管一些全基因组扫描已经确定了影响人类几种肥胖相关性状的数量性状基因座，但影响肥胖表型正常变异的基因尚未确定。因此，我们对墨西哥裔美国人（易患肥胖和糖尿病的人群）进行了体重指数 (BMI) 的基因组扫描，使用方差分量连锁分析来识别影响 BMI 的位点。我们使用了 430 名个体（26% 糖尿病患者，59% 女性，平均年龄+/-SD=43+/-17 岁，平均 BMI+/-SD=30.0+/-6.7，平均瘦素 (ng/ml)+/-SD=22.1+/-17.1）的表型数据，这些人分布在参与圣安东尼奥家庭糖尿病的 27 个低收入墨西哥裔美国人谱系中 研究 (SAFDS) 可为谁提供 10-15-cM 地图。在这项全基因组搜索中，在考虑了年龄、性别、糖尿病和瘦素的协变量影响后，我们发现了一个基因区域，该区域表现出与 4p 染色体 4p (4p15.1) 上 42 cM 处的 BMI 连锁 (LOD 4.5) 最显着的证据，靠近标记 D4S2912。这一连锁结果已在犹他州谱系中严重肥胖的独立连锁研究中得到证实。两个强有力的候选位置，人过氧化物酶体增殖物激活受体 γ 共激活因子 1 (PPARGC1) 和胆囊收缩素 A 受体 (CCKAR)，在肥胖的发展中发挥着重要作用，位于该区域。总之，我们在墨西哥裔美国人的 4p 染色体上确定了影响 BMI 的主要遗传位点。
Although several genomewide scans have identified quantitative-trait loci influencing several obesity-related traits in humans, genes influencing normal variation in obesity phenotypes have not yet been identified. We therefore performed a genome scan of body mass index (BMI) on Mexican Americans, a population prone to obesity and diabetes, using a variance-components linkage analysis to identify loci that influence BMI. We used phenotypic data from 430 individuals (26% diabetics, 59% females, mean age+/-SD=43+/-17 years, mean BMI+/-SD=30.0+/-6.7, mean leptin (ng/ml)+/-SD=22.1+/-17.1) distributed across 27 low-income Mexican American pedigrees who participated in the San Antonio Family Diabetes Study (SAFDS) for whom a 10-15-cM map is available. In this genomewide search, after accounting for the covariate effects of age, sex, diabetes, and leptin, we identified a genetic region exhibiting the most highly significant evidence for linkage (LOD 4.5) with BMI on chromosome 4p (4p15.1) at 42 cM, near marker D4S2912. This linkage result has been confirmed in an independent linkage study of severe obesity in Utah pedigrees. Two strong positional candidates, the human peroxisome proliferator-activated receptor gamma coactivator 1 (PPARGC1) and cholecystokinin A receptor (CCKAR) with major roles in the development of obesity, are located in this region. In conclusion, we identified a major genetic locus influencing BMI on chromosome 4p in Mexican Americans.