[Association between rs10938397 polymorphism in GNPDA2 and obesity in children at different stages of development].

Objective: To examine the association between rs10938397 polymorphism in glucosamine-6-phosphate deaminase 2 (GNPDA2) and risk of obesity in children at different stages of development and analyze the differences in the association. Methods: A total of 3 503 school-aged children were selected from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study in Beijing and their complete anthropometry weight, height, fat mass percentage (FMP), fat mass index (FMI) and free fat mass index (FFMI) and sexual maturation (SM) data were used. The developmental stages were evaluated using male testicular volume and female breast Tanner staging. FMP, FM and FFM were measured by bioelectrical impedance analysis. General obesity and adiposity were respectively defined according to Chinese sex-age-specific body mass index (BMI) cutoffs and sex-age-specific FMP cutoffs. The SNP rs10938397 were genotyped by the TaqMan Allelic Discrimination Assay with the GeneAmp 7900 sequence detection system (Applied Biosystems, Foster city, CA, USA). Relationships between rs10938397 polymorphism and BMI, FMP, FMI and FFMI and different types of obesity were tested using multivariate linear regression and logistic regression models. Results: After age adjustment and correction for multiple testing, the rs10938397-G was associated with BMI and risk of general obesity in boys in early puberty (β=0.328, P=0.001; OR=1.420, 95%CI: 1.126-1.790), and the rs10938397-G was associated with BMI in girls in late puberty (β=0.266, P=0.001). The associations of GNPDA2 rs10938397-G with FFMI and FMI were observed in boys in early puberty (β=0.137, P=0.016; β=0.202, P=0.007) and the associations of rs10938397-G with FMP and FMI were observed in girls in late puberty (β=0.153, P=0.002; β=0.168, P=0.001). The rs10938397-G was also associated with adiposity in girls in late puberty (OR=1.339, 95%CI: 1.093-1.637). Conclusion: The rs10938397 polymorphism in GNPDA2 is associated with adiposity in girls, and it is important to use an accurate indicator of obesity in exposing the genuine association between genes and obesity.目的： 探讨葡萄糖胺-6-磷酸盐脱氨酶-2基因（GNPDA2）rs10938397多态性与不同发育阶段儿童肥胖的关联性，并分析差异原因。 方法： 利用北京儿童青少年代谢综合征研究（BCAMS）的3 503名6~18岁中小学生的青春期发育、BMI、体脂百分比（FMP）、脂肪指数（FMI）和非脂肪指数（FFMI）等数据。采用男性睾丸容积和女性乳房Tanner分期指标衡量发育阶段。生物电阻抗法测定FMP、脂肪质量（FM）和非脂肪质量（FFM）。采用肥胖问题工作组推荐的BMI分类标准判定一般性肥胖，采用儿童少年卫生学推荐的FMP分类标准判定体脂肥胖。使用ABI Prisms(TM)-7900实时荧光定量PCR仪对GNPDA2 rs10938397进行分型。分别采用多元线性回归和非条件logistic回归分析rs10938397多态性与连续性变量（BMI、FMP、FMI、FFMI）和分类变量（一般性肥胖、体脂肥胖）的关系。 结果： 青春发育前期男生rs10938397-G与BMI和一般性肥胖关联（β=0.328，P=0.001；OR=1.420，95% CI：1.126~1.790）有统计学意义，青春发育后期女生rs10938397-G与BMI和一般性肥胖关联（β=0.266，P=0.001；OR=1.442，95%CI：1.005~2.069）有统计学意义。采用错误发现率（FDR）方法校正多重检验，青春发育后期女生该位点与一般性肥胖的关联消失。进一步分析GNPDA2 rs10938397-G等位基因与不同发育阶段儿童FMP、FMI、FFMI的关联，结果显示：GNPDA2 rs10938397-G与青春发育前期男生FMP、FMI和FFMI密切关联（β=0.165，P=0.032；β=0.202，P=0.007；β=0.137，P=0.016），与青春发育后期女生FMP和FMI密切关联（β=0.153，P=0.002；β=0.168，P=0.001）。此外，位点与体脂肥胖关联见于青春发育前期男生（OR=1.285，95% CI：1.009~1.637）和青春发育后期女生（OR=1.339，95% CI：1.093~1.637）。采用FDR校正多重检验，青春发育前期男生rs10938397与FMP和体脂肥胖关联消失。 结论：GNPDA2基因rs10938397多态性与女生以体脂增加为表现的真实性肥胖具有关联。对于揭露基因与肥胖的真实关联，更准确地评价肥胖状况十分重要。.