Genomic scan of glucose and insulin metabolism phenotypes: The HERITAGE family study
Genomic scan of glucose and insulin metabolism phenotypes: The HERITAGE family study
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DOI：
10.1053/meta.2003.50030
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发表时间：
2003-02-01
影响因子：
9.8
通讯作者：
Rao, DC
中科院分区：
文献类型：
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作者：
An, P;Hong, YL;Rao, DC
遗传因素在葡萄糖代谢相关性状如胰岛素敏感性（SI）、胰岛素分泌和葡萄糖有效性（S(;)）的调控中发挥作用。已经进行了几次基因组扫描来定位涉及葡萄糖代谢相关特征的基因。然而，这些研究中很少有使用最小建模（MINMOD）方法从频繁采样的静脉内葡萄糖耐量试验（IVGTT）中获得的表型。在这里，我们报告了这种葡萄糖代谢相关特征的扫描，这些特征来自于对来自95个久坐白人家庭的322对兄弟姐妹和来自49个久坐黑人家庭的75对兄弟姐妹的IVGTT数据的MINMOD分析。除了S-I和S-G，我们还考虑了急性胰岛素对葡萄糖挑战的反应（AIR（葡萄糖）），这是胰岛素分泌的指标，以及处置指数（DI， S-1和AIR（葡萄糖）的产物），这是胰岛素抵抗后胰腺细胞活性的量度。这些性状根据年龄、性别和体重指数（BMI）在8个性别-代际-种族组中进行调整，然后使用标准化残差作为连锁分析中的表型。采用计算机程序SEGPATH中实现的多点方差成分联系法，使用509个标记进行分析。几个有希望联系的地区(LOD评分大于或等于1.75，小于或等于。0023)被检测到。它们包括白人中的5个区域（S-1的1q41和8p23.2， AIR（葡萄糖）的4q32.1和10p15.3， DI的13q32.1）和黑人中的2个区域（S-1的9p11.2和10q26.11）。这些区域中的三个（4q32.1, 9p11.2, 10p15.3）可能包含影响葡萄糖代谢相关性状个体间差异的基因，因为它们重复了其他研究的发现。这些基因组区域内候选基因的精细定位和关联研究是必要的。版权所有，爱思唯尔科学（美国）。版权所有。
Genetic factors play a role in the regulation of glucose metabolism-related traits such as insulin sensitivity (SI), insulin secretion, and glucose effectiveness (S(;). Several genomic scans have been performed to localize genes involved in glucose metabolism-related traits. However, few of these studies have been performed with phenotypes derived from the frequently sampled intravenous glucose tolerance test (IVGTT) using the minimal modeling (MINMOD) approach. Here, we report on such a scan for glucose metabolism-related traits derived from MINMOD analysis of IVGTT data in 322 sibling pairs from 95 sedentary white families and 75 sibling pairs from 49 sedentary black families from the HERITAGE Family Study. In addition to S-I and S-G, we also considered acute insulin response to a glucose challenge (AIR(Glucose)), which is an index for insulin secretion, and disposition index (DI, product of S-1 and AIR(Glucose)), which is a measure of the activity of pancreatic 13 cells corrected for insulin resistance. These traits were adjusted for age, sex, and body mass index (BMI) in each of 8 sex-by-generation-by-race groups, and then standardized residuals were used as the phenotypes in the linkage analyses. Analyses were with the multipoint variance components linkage method, as implemented in the computer program SEGPATH, using 509 markers. Several regions with promising linkages (LOD score greater than or equal to 1.75, Pless than or equal to.0023) were detected. They include five regions (1q41 and 8p23.2 for S-1, 4q32.1 and 10p15.3 for AIR(Glucose), and 13q32.1 for DI) in whites and 2 regions (9p11.2 for SG and 10q26.11 for S-1) in blacks. Three of these regions (4q32.1, 9p11.2, 10p15.3) are likely to harbor genes that influence interindividual variation in glucose metabolism-related traits as they replicate findings from other studies. Fine mapping and association studies of candidate genes within these genomic regions are warranted. Copyright 2003, Elsevier Science (USA). All rights reserved.