Fuemmeler Bernard F, Agurs-Collins Tanya D, McClernon F Joseph, Kollins Scott H, Kail Melanie E, Bergen Andrew W, Ashley-Koch Allison E
Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA.
Obesity (Silver Spring). 2008 Feb;16(2):348-55. doi: 10.1038/oby.2007.65.
This study addressed the hypothesis that variation in genes associated with dopamine function (SLC6A3, DRD2, DRD4), serotonin function (SLC6A4, and regulation of monoamine levels (MAOA) may be predictive of BMI categories (obese and overweight + obese) in young adulthood and of changes in BMI as adolescents transition into young adulthood. Interactions with gender and race/ethnicity were also examined.
Participants were a subsample of individuals from the National Longitudinal Study of Adolescent Health (Add Health), a nationally representative sample of adolescents followed from 1995 to 2002. The sample analyzed included a subset of 1,584 unrelated individuals with genotype data. Multiple logistic regressions were conducted to evaluate the associations between genotypes and obesity (BMI > 29.9) or overweight + obese combined (BMI > or = 25) with normal weight (BMI = 18.5-24.9) as a referent. Linear regression models were used to examine change in BMI from adolescence to young adulthood.
Significant associations were found between SLC6A4 5HTTLPR and categories of BMI, and between MAOA promoter variable number tandem repeat (VNTR) among men and categories of BMI. Stratified analyses revealed that the association between these two genes and excess BMI was significant for men overall and for white and Hispanic men specifically. Linear regression models indicated a significant effect of SLC6A4 5HTTLPR on change in BMI from adolescence to young adulthood.
Our findings lend further support to the involvement of genes implicated in dopamine and serotonin regulation on energy balance.
本研究探讨了以下假设，即与多巴胺功能相关的基因（SLC6A3、DRD2、DRD4）、血清素功能相关的基因（SLC6A4）以及单胺水平调节基因（MAOA）的变异可能预测青年期的BMI类别（肥胖以及超重+肥胖），以及青少年向青年期过渡过程中BMI的变化。同时还研究了这些基因与性别和种族/族裔的相互作用。
参与者是青少年健康全国纵向研究（Add Health）中的一个子样本，该研究是对1995年至2002年期间具有全国代表性的青少年样本进行跟踪调查。分析的样本包括1584名具有基因型数据的无亲属关系个体的子集。进行了多项逻辑回归分析，以评估基因型与肥胖（BMI>29.9）或超重+肥胖合并（BMI≥25）与正常体重（BMI=18.5-24.9）之间的关联，以正常体重作为对照。使用线性回归模型来研究从青少年到青年期BMI的变化。
发现SLC6A4 5HTTLPR与BMI类别之间存在显著关联，并且男性中MAOA启动子可变数目串联重复序列（VNTR）与BMI类别之间也存在显著关联。分层分析表明，这两个基因与超重BMI之间的关联在总体男性中以及特别是白人和西班牙裔男性中具有显著性。线性回归模型表明，SLC6A4 5HTTLPR对从青少年到青年期BMI的变化具有显著影响。
我们的研究结果进一步支持了涉及多巴胺和血清素调节的基因对能量平衡的影响。
