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Assessing Sequence Variations in the Leptin Gene in African Americans

机译:评估非洲裔美国人瘦素基因的序列变异

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Obesity has become the nation's number one health issue and is impacted by factors such as genetic predisposition, nutrition, and environment. Sixty-five percent of American adults are overweight or obese, and the rate has more than doubled (15%) in children ages 6-11. Leptin, an adipo-cyte-derived peptidic hormone and product of the obesity gene, has been linked to several diseases such as obesity, diabetes, heart disease, post-menopausal breast cancer, pituitary dysfunction, infertility, and bone density. Cloning of the ob (lep) gene has greatly advanced our understanding of the mechanisms involving obesity. Leptin is encoded by a gene located on human chromosome 7q31.3 and demonstrates structural similarities with the cytokine family. Research has shown that sequence variants in the 5' flanking region of lep gene were found to be associated with obesity. Rare forms of human obesity have now been identified where mutations in leptin receptors might play a major role in the development of the disease. These previous studies involving obesity included few African American participants. Therefore, the present study under Project EXPORT focuses on the molecular aspect of obesity in African Americans as a health disparity of major concern. The research correlates serum parameters with SNP's in the leptin gene. The 120 subjects were categorized based on age and weight with 17% normal, 27% overweight, and 56% obese. PCR tests were used to screen 120 participants' DNA with primers specific to the Lep gene. For the Lep gene, the expected 242 bp fragment was digested with Cfo I to yield three bands (242, 181, and 61 bp) indicating a single nucleotide (G to A) polymorphism at locus 2548 in the promoter of the Lep gene. The pathogenicity of obese people in this study follows the same pattern as the national obesity prevalence in minority communities. Tuskegee University Project EXPORT/NIH-NCMHD.
机译:肥胖已成为美国第一大健康问题,并且受到遗传易感性,营养和环境等因素的影响。 65%的美国成年人超重或肥胖,在6至11岁的儿童中,这一比例增加了一倍多(15%)。瘦素是由脂肪细胞产生的肽激素,是肥胖基因的产物,已与多种疾病有关,例如肥胖,糖尿病,心脏病,绝经后乳腺癌,垂体功能障碍,不育症和骨密度。 ob(lep)基因的克隆大大提高了我们对涉及肥胖的机制的理解。瘦素由位于人类染色体7q31.3上的一个基因编码,并显示出与细胞因子家族的结构相似性。研究表明,发现lep基因5'侧翼区域的序列变异与肥胖有关。现在已经鉴定出稀有形式的人类肥胖症,其中瘦素受体的突变可能在疾病的发展中起主要作用。这些涉及肥胖的先前研究几乎没有非洲裔美国人参加。因此,本项目EXPORT下的研究集中在非裔美国人肥胖的分子方面,这是主要关注的健康差距。这项研究将瘦素基因中的血清参数与SNP相关联。根据年龄和体重对120位受试者进行了分类,其中正常人群为17%,超重人群为27%,肥胖人群为56%。 PCR测试用于筛选Lep基因特异性引物的120位参与者的DNA。对于Lep基因,用Cfo I消化了预期的242 bp片段,产生了三个条带(242、181和61 bp),表明Lep基因的启动子在基因座2548具有单核苷酸(G到A)多态性。在这项研究中,肥胖人群的致病性与少数民族社区中的全国肥胖流行率相同。塔斯基吉大学项目EXPORT / NIH-NCMHD。

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