胰岛素敏感性和胰岛素清除率具有遗传性，且在墨西哥裔美国人中存在很强的遗传相关性。
Insulin sensitivity and insulin clearance are heritable and have strong genetic correlation in Mexican Americans.
作者信息
Goodarzi Mark O, Langefeld Carl D, Xiang Anny H, Chen Yii-Der I, Guo Xiuqing, Hanley Anthony J G, Raffel Leslie J, Kandeel Fouad, Nadler Jerry L, Buchanan Thomas A, Norris Jill M, Fingerlin Tasha E, Lorenzo Carlos, Rewers Marian J, Haffner Steven M, Bowden Donald W, Rich Stephen S, Bergman Richard N, Rotter Jerome I, Watanabe Richard M, Wagenknecht Lynne E
机构信息
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA; Medical Genetics Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
出版信息
Obesity (Silver Spring). 2014 Apr;22(4):1157-64. doi: 10.1002/oby.20639.
OBJECTIVE
The GUARDIAN (Genetics UndeRlying DIAbetes in HispaNics) consortium is described, along with heritability estimates and genetic and environmental correlations of insulin sensitivity and metabolic clearance rate of insulin (MCRI).
METHODS
GUARDIAN is comprised of seven cohorts, consisting of 4,336 Mexican-American individuals in 1,346 pedigrees. Insulin sensitivity (SI ), MCRI, and acute insulin response (AIRg) were measured by frequently sampled intravenous glucose tolerance test in four cohorts. Insulin sensitivity (M, M/I) and MCRI were measured by hyperinsulinemic-euglycemic clamp in three cohorts. Heritability and genetic and environmental correlations were estimated within the family cohorts (totaling 3,925 individuals) using variance components.
RESULTS
Across studies, age, and gender-adjusted heritability of insulin sensitivity (SI , M, M/I) ranged from 0.23 to 0.48 and of MCRI from 0.35 to 0.73. The ranges for the genetic correlations were 0.91 to 0.93 between SI and MCRI; and -0.57 to -0.59 for AIRg and MCRI (all P < 0.0001). The ranges for the environmental correlations were 0.54 to 0.74 for SI and MCRI (all P < 0.0001); and -0.16 to -0.36 for AIRg and MCRI (P < 0.0001-0.06).
CONCLUSIONS
These data support a strong familial basis for insulin sensitivity and MCRI in Mexican Americans. The strong genetic correlations between MCRI and SI suggest common genetic determinants.
目的
介绍西班牙裔人群糖尿病遗传因素（GUARDIAN）联盟，以及胰岛素敏感性和胰岛素代谢清除率（MCRI）的遗传度估计值、遗传和环境相关性。
方法
GUARDIAN联盟由7个队列组成，包括1346个家系中的4336名墨西哥裔美国人。在4个队列中，通过频繁采样静脉葡萄糖耐量试验测量胰岛素敏感性（SI）、MCRI和急性胰岛素反应（AIRg）。在3个队列中，通过高胰岛素-正常血糖钳夹技术测量胰岛素敏感性（M、M/I）和MCRI。使用方差成分法在家族队列（共3925人）中估计遗传度、遗传和环境相关性。
结果
在各项研究中，经年龄和性别调整后，胰岛素敏感性（SI、M、M/I）的遗传度范围为0.23至0.48，MCRI的遗传度范围为0.35至0.73。SI与MCRI之间的遗传相关性范围为0.91至0.93；AIRg与MCRI之间的遗传相关性范围为-0.57至-0.59（所有P<0.0001）。SI与MCRI之间的环境相关性范围为0.54至0.74（所有P<0.0001）；AIRg与MCRI之间的环境相关性范围为-0.16至-0.36（P<0.0001至0.06）。
结论
这些数据支持墨西哥裔美国人胰岛素敏感性和MCRI存在强大的家族基础。MCRI与SI之间的强遗传相关性表明存在共同的遗传决定因素。
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