Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome
Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome
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DOI：
10.1073/pnas.97.26.14478
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发表时间：
2000-12-19
影响因子：
11.1
通讯作者：
Comuzzie, AG
中科院分区：
文献类型：
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作者：
Kissebah, AH;Sonnenberg, GE;Comuzzie, AG
最近的研究强调了代谢簇的重要性，包括葡萄糖耐量异常、血脂异常和高血压，作为肥胖相关疾病和过早死亡的强烈预测因子。这种联系的基础，通常被称为代谢综合征，是腹部脂肪模式、全身肥胖和胰岛素抵抗之间的密切相互作用。作为确定影响这些表型的主要遗传基因座的第一步，我们使用10厘米摩根图谱对分布在507个高加索核心家庭的2209个个体进行了全基因组扫描。使用方差成分连锁模型进行的系谱分析表明，染色体3(3q27)上的一个数量性状基因座(QTL)与代表这些基本表型的6个性状密切相关[优势对数(LOD)分数从2.4到3.5]。该QTL可能与17号染色体上的第二个QTL(17p12)存在上位性互作，该QTL与血浆瘦素水平密切相关(LOD=5.0)。位于这些上位性QTL的候选基因可能影响代谢综合征的两条生物前体途径。
Recent research has emphasized the importance of the metabolic cluster, which includes glucose intolerance, dyslipidemia, and high blood pressure, as a strong predictor of the obesity-related morbidities and premature mortality. Fundamental to this association, commonly referred to as the metabolic syndrome, is the close interaction between abdominal fat patterning, total body adiposity, and insulin resistance. As the initial step in identifying major genetic loci influencing these phenotypes, we performed a genomewide scan by using a 10-centiMorgan map in 2,209 individuals distributed over 507 nuclear Caucasian families. Pedigree-based analysis using a variance components linkage model demonstrated a quantitative trait locus (QTL) on chromosome 3 (3q27) strongly linked to six traits representing these fundamental phenotypes [logarithm of odds (lod) scores ranged from 2.4 to 3.5]. This QTL exhibited possible epistatic interaction with a second QTL on chromosome 17 (17p12) strongly linked to plasma leptin levels (lod = 5.0). Situated at these epistatic QTLs are candidate genes likely to influence two biologic precursor pathways of the metabolic syndrome.