Using genetic admixture to explain racial differences in insulin-related phenotypes
Using genetic admixture to explain racial differences in insulin-related phenotypes
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DOI：
10.2337/diabetes.52.4.1047
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发表时间：
2003-04-01
期刊：
影响因子：
7.7
通讯作者：
Goran, MI
中科院分区：
文献类型：
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作者：
Gower, BA;Fernández, JR;Goran, MI
非裔美国人和欧裔美国人在胰岛素分泌和作用的测量方面存在有记录的差异，这可能是由于遗传因素或环境因素造成的。本研究利用从约20个祖先信息标记确定的遗传混合（ADM）以及一份旨在评估社会经济地位（SES）的问卷，对居住在阿拉巴马州伯明翰的125名儿童进行研究，以检验遗传和环境因素对最小模型衍生的胰岛素敏感性（S - I）、空腹胰岛素以及葡萄糖急性胰岛素反应（AIR(g)）测量值的潜在影响。该研究采用纵向设计，对每个研究对象都有多个结果测量值。在对混杂因素（青春期状态、肥胖程度、年龄）以及个体的重复测试进行调整后，使用混合模型分析来确定ADM和SES是否分别与S - I、空腹胰岛素以及AIR(g)相关。在这个队列中，非洲遗传混合比例从0%（没有反映非洲血统标记的个体）到100%（所有20个标记都反映非洲血统的个体）不等。结果表明，ADM与S - I（P < 0.001）和空腹胰岛素（P < 0.01）独立相关，非洲遗传混合比例较高的个体S - I较低，空腹胰岛素浓度较高。ADM（P < 0.001）和SES（P < 0.05）都与AIR(g)独立相关；即使在对S - I进行调整后，非洲遗传混合比例较高或SES较低的儿童AIR(g)也较高。这些观察结果表明，使用ADM可以取代将个体归入种族类别；与欧裔美国人相比，非裔美国人中较低的S - I和较高的空腹胰岛素可能有遗传基础；非裔美国人中较高的AIR(g)可能是由于遗传因素以及尚未确定的环境因素共同导致的。
Documented differences in measures of insulin secretion and action between African Americans and European Americans may be due to either genetic or environmental factors. This study used genetic admixture (ADM), determined from similar to20 ancestry informative markers, and a questionnaire designed to assess socioeconomic status (SES) to examine potential genetic and environmental contributions to minimal model-derived measures of insulin sensitivity (S-I), fasting insulin, and the acute insulin response to glucose (AIR(g)) in 125 children residing in Birmingham, Alabama. The study was longitudinal in design and yielded multiple outcome measures on each subject. Mixed models analysis was used to determine if ADM and SES were independently related to S-I, fasting insulin, and AIR(g) after adjusting for confounding factors (pubertal status, adiposity, age) and for repeated testing of individuals. In this cohort, African ADM ranged from 0% (individuals with no markers reflecting African ancestry) to 100% (individuals with all 20 markers reflecting African ancestry). Results indicated that ADM was independently related to S-I (P < 0.001) and fasting insulin (P < 0.01), with individuals having greater African ADM having a lower S, and a higher fasting insulin concentration. Both ADM (P < 0.001) and SES (P < 0.05) were independently related to AIR(g); children with greater African ADM or lower SES had a higher AIR(g), even after adjusting for S-I These observations suggest that use of ADM can replace assignment of individuals to categorical racial groups; that lower S-I and higher fasting insulin among African Americans compared with European Americans may have a genetic basis; and that higher AIR(g) among African Americans may be due to both genetic factors and to environmental factors that remain to be identified.