A major susceptibility locus influencing plasma triglyceride concentrations is located on chromosome 15q in Mexican Americans
A major susceptibility locus influencing plasma triglyceride concentrations is located on chromosome 15q in Mexican Americans
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DOI：
10.1086/302849
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发表时间：
2000-04-01
影响因子：
9.8
通讯作者：
Stern, MP
中科院分区：
文献类型：
--
作者：
Duggirala, R;Blangero, D;Stern, MP
尽管已经报道了几种罕见或综合征性高胆固醇血症的遗传形式，但对携带常见形式高胆固醇血症易感基因的基因组中的特定染色体区域知之甚少。因此，我们在墨西哥裔美国人群体中进行了影响血浆甘油三酯（TG）水平的易感基因的全基因组扫描。我们使用的表型和基因型数据来自418个人分布在27个低收入，扩大墨西哥裔美国人家庭。对于分析，对TG值进行对数转换（以TC计）。我们使用方差分量技术进行多点连锁分析，定位决定TG水平变化的易感基因。我们使用了一个类似于10-15-cM的图谱，该图谱是根据295个微卫星标记的信息制作的。在考虑性别和性别特异性年龄项的影响后，我们发现了显着的证据连锁（LOD = 3.88）的TG水平之间的标记GABRB 3和D15 S165染色体15 q的遗传位置。这个假定的基因座解释了TG水平总表型变异的39.7 +/- 7%（P = 0.000012）。暗示的证据被发现的连锁的TG水平的两个不同的位置上的7号染色体，这是类似的85厘米，彼此分开。此外，有一些证据表明高密度脂蛋白胆固醇浓度与7号染色体上某个区域附近的遗传位置有关。总之，我们发现了强有力的证据表明，在TG水平的连锁遗传位置染色体15 q的墨西哥裔美国人的人口，这是容易患疾病的条件，如2型糖尿病和胰岛素抵抗综合征，与高血糖症。这个假定的基因座似乎有一个重大的影响，在TG的变化。
Although several genetic forms of rare or syndromic hypertriglyceridemia have been reported, little is known about the specific chromosomal regions across the genome harboring susceptibility genes for common forms of hypertriglyceridemia. Therefore, we conducted a genomewide scan for susceptibility genes influencing plasma triglyceride (TG) levels in a Mexican American population. We used both phenotypic and genotypic data from 418 individuals distributed across 27 low-income, extended Mexican American families. For the analyses, TG values were log transformed (In TC). We used a variance-components technique to conduct multipoint linkage analyses for localizing susceptibility genes that determine variation in TG levels. We used an similar to 10-15-cM map, which was made on the basis of information from 295 microsatellite markers. After accounting for the effects of sex and sex-specific age terms, we found significant evidence for linkage (LOD = 3.88) of In TG levels to a genetic location between the markers GABRB3 and D15S165 on chromosome 15q. This putative locus explains 39.7 +/- 7% (P = .000012) of total phenotypic variation in In TG levels. Suggestive evidence was found for linkage of In TG levels to two different locations on chromosome 7, which are similar to 85 cM apart from each other. Also, there is some evidence for linkage of high-density lipoprotein cholesterol concentrations to a genetic location near one of the regions on chromosome 7. In conclusion, we found strong evidence for linkage of In TG levels to a genetic location on chromosome 15q in a Mexican American population, which is prone to disease conditions such as type 2 diabetes and the insulin-resistance syndrome that are associated with hypertriglyceridemia. This putative locus appears to have a major influence on In TG variation.