儿童青少年双生子胰岛素敏感性的遗传度估计及影响因素分析

目的:分析影响儿童青少年的胰岛素敏感性的遗传和环境因素,并探讨其中体质指数(body mass index, BMI)、年龄和性别的作用.方法:选择5～18岁同性别双生子296对,平均年龄(12.4±3.5)岁,其中同卵双生子(MZ)223对,异卵双生子(DZ)73对.在DNA卵性鉴定基础上,应用Mx软件模型拟合分别计算BMI调整前后稳态模型胰岛素抵抗指数(homeostasis model assessment insulin resistance index, HOMA IR)和β细胞功能指数(HOMA β-cell function index,HBCI)的遗传度,并检验年龄和性别对于模型的作用.结果:HOMA IR与年龄、性别和BMI相关,HBCI与年龄相关,遗传分析HOMA IR、HBCI的模型为ACE,BMI调整前后HOMA IR男女生遗传度不同,HBCI无明显变化.调整后HOMA IR、HBCI遗传度分别为0.25、0.24.结论:儿童青少年人群中HOMA IR、HBCI受遗传和环境因素共同作用,环境因素的影响似乎更大;BMI是影响机体胰岛素敏感性的重要因素;年龄和性别对遗传度的影响可能不大.

Heritability analysis of insulin sensitivity and the effect of age and sex: a twin study in Chinese aged 5-18

OBJECTIVE: To study the contribution of genes and environment to the variation of insulin sensitivity, and the effect of body mass index (BMI), age and sex. METHODS: A total of 296 healthy same-sex twin pairs were studied, including 223 monozygotic (MZ) and 73 dizygotic (DZ) twin pairs aged 5-18(mean age, 12+/-4 years). Microsatellite polymorphism (STR) was used to diagnose zygosity of twins. Model-fitting method using Mx package was performed to analyze the genetic and environmental variance of homeostasis model assessment insulin resistance index (HOMA IR) and HOMA beta cell function index (HBCI), before and after adjusting BMI. The effect of age and sex on the model was tested. RESULTS: HOMA IR was correlated with age, sex and BMI, while HBCI was correlated with age. Genetic analysis showed in ACE model, heritability of HOMA IR in boys and girls was different before and after BMI adjustment; heritability of HBCI was not different significantly. Heritability of HOMA IR and HBCI were 0.25, 0.24, respectively, after adjusting BMI. CONCLUSION: Gene and environment influence insulin sensitivity of children and adolescents together, whereas environment seems to play a more important role. The effect of BMI on estimating heritability of insulin sensitivity is considerable, differing from sex or age.