遗传易感性和早期生活方式的交互作用在婴幼儿肥胖发生中的作用

Childhood obesity has become a major public health concern worldwide, and it has serious adverse impacts on the health of children and the quality of their lives. China has also witnessed its rapid increasing tendency. Obesity is a complex trait that stems from the interaction of complicated network involving genomic and environmental factors. The role of this complex interaction in early childhood obesity remains unknown.A total of 1000 pairs of high exposure (children with both parents being overweight or at least one being obese) and low exposure children (children with normal weight parents) are to be selected from an infant birth cohort constituting 10,000 children in Wuhan. The candidate SNPs are determined according to the latest results from GWAS and the latest Meta analysis of BMI-related genes of Asian ancestry (GWAS data came from the Asian Genetic Epidemiology Network (AGEN) BMI-Consortium). By Using TaqMan Openarray genotyping technique, genotype variation is to be detected and its comparison made between the high and low exposure groups. Simultaneously the physical development and early life style variables in children are to be collected, with the use of biostatistics and bioinformation analysis, to explore the interaction of genes and life style factors on children BMI as well as the development of obesity. The results from the above cohort will be verified in the birth cohorts in cities of Ezhou and Macheng.The results are expected to provide an insight into the etiological mechanism for early-onset of childhood obesity, and therefore contribute to the early detection of high risk children and the development of a more feasible and effective intervention strategy.

儿童肥胖是全球范围内的重大公共卫生问题,在我国呈现快速上升趋势，严重影响儿童远近期健康和生命质量。肥胖是环境与基因交互作用的共同产物，而其交互作用在儿童早期肥胖发生中的作用尚不明确。研究在武汉市10000名婴儿出生队列人群中，选择1000对高暴露组（父母双方超重/至少一方肥胖）和低暴露组（父母体重正常）儿童,动态采集儿童早期生活方式和体格发育数据；根据GWAS研究进展和亚洲人群BMI相关基因Meta分析结果，综合选定候选单核苷酸多态性位点（SNPs），利用TaqMan Openarray基因分型技术检测生物样品，比较和发现两组儿童遗传变异；采用生物统计学和生物信息学方法，系统分析早期生活方式和基因的交互作用对儿童BMI的影响及其在肥胖发生中的作用。重要发现将在鄂州和麻城的队列人群中予以验证。本研究结果将加深对儿童早期肥胖机制的理解，为高危人群的早期发现和制定早期预防对策提供科学依据。

儿童肥胖危害严重，已成为严重影响我国人口质量和经济发展的重大公共卫生问题。作为一个复杂的医学问题，肥胖是遗传、环境因素及彼此交互作用的共同产物，但其交互作用仍不清楚。本研究利用珠海母婴队列研究，采用基因分型技术对综合选定的12个候选SNPs进行基因分型，探讨基因、环境因素及两者交互作用对儿童肥胖的影响。本研究发现，父母BMI对儿童多个月龄BMI_Z均有显著性影响，且父母体重状态和喂养模式对儿童各月龄BMI_Z影响具有统计学差异。校正混杂因素影响后，母亲孕前低体重的儿童1、3、6、12月龄BMI_Z低于母亲孕前体重正常组儿童；母亲孕前超重/肥胖的儿童各月龄BMI_Z较母亲孕前体重正常组呈现增高趋势，其中6、12月龄BMI_Z在两组间差异有统计学意义；与父亲正常体重组相比，父亲超重组儿童各月龄BMI_Z有增高的趋势。孕期体重增长与儿童1月龄和12月龄BMI_Z有统计学关联性。1月龄混合喂养和人工喂养分别与1月龄和6月龄BMI_Z有显著性负向关联和正向关联；6月龄时，人工喂养的儿童较纯母乳喂养的儿童BMI_Z更低。0～3月龄儿童体重增速过快或过慢均影响儿童6、12月龄时BMI_Z。单个SNP位点分析时发现SEC16B rs574367、rs543874和BDNF rs11030104与12月龄儿童超重/肥胖风险有关。母亲孕前体重状态与SEC16B rs543874的交互作用与12月龄儿童超重/肥胖有显著性关联。决策树分析发现BDNF rs11030104、SEC16B rs10913469 和rs543874、NT5C2 rs11191580、PTBP2 rs11165675等5个位点对儿童肥胖存在显著的交互影响。其中，携带超过3个风险基因型的个体，其超重/肥胖风险是不携带风险基因型者的4.50倍（OR=4.50，95%CI：2.16～9.36）。本研究结果表明，超重/肥胖是珠海市0～12月龄儿童生长偏离的主要问题。在进行婴儿生长发育评估及体格生长偏离干预时，需考虑不同时期各因素（父亲和母亲孕前体重状态、母亲孕期体重增长、婴儿早期喂养方式及早期体重增长模式、基因多态性及其与环境因素交互作用）对超重/肥胖影响大小的差异。还需要更大样本的流行病学研究来验证本研究结果。