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脑源性神经营养因子 Val66Met 多态性与儿科人群超重/肥胖的关联。

Association Between the Brain-derived Neurotrophic Factor Val66Met Polymorphism and Overweight/Obesity in Pediatric Population.

机构信息

Unidad de Investigación Médica en Genética Humana, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México; Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Av. Ciudad Universitaria, Coyoacán, Ciudad de México, México.

Unidad de Investigación en Epidemiología Clínica, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México.

出版信息

Arch Med Res. 2017 Oct;48(7):599-608. doi: 10.1016/j.arcmed.2018.02.005. Epub 2018 Mar 3.

Abstract

BACKGROUND

The brain-derived neurotrophic factor (BDNF) rs6265 (G196A; Val66Met) single nucleotide polymorphism has been associated with BMI and obesity in distinct populations, both adult and pediatric, with contradictory results involving either Val or Met as the risk variant.

AIM OF THE STUDY

To determine the association between the BDNF Val66Met polymorphism and BMI in Mexican children and adolescents.

METHODS

BDNF Val66Met genotyping by restriction fragment length polymorphism and nutritional status characterized by their BMI-for-age z-scores (BAZ) from pediatric volunteers (n = 498) were analyzed by Fisher's exact test association analysis. Standardized residuals (R) were used to determine which genotype/allele had the major influence on the significant Fisher's exact test statistic. Odds ratios were analyzed to measure the association between genotype and normal weight (≥-2 SD < + 1 SD) and overweight (≥ + 1 SD, including obesity, Ow + Ob) status with 95% confidence intervals to estimate the precision of the effect as well as 95% credible intervals to obtain the most probable estimate.

RESULTS

Comparisons between GG (Val/Val), GA (Val/Met) and AA (Met/Met) genotypes or Met homozygotes vs. Val carriers (combination of GG and GA genotypes) showed significant differences (p = 0.034 and p = 0.037, respectively) between normal weight and the combined overweight and obese pediatric subjects. Our data showed that children/adolescents homozygous for the A allele have increased risk of overweight compared to the Val carriers (Bayes OR = 4.2, 95% CI**[1.09-33.1]).

CONCLUSION

This is the first study showing the significant association between the BDNF rs6265 AA (Met/Met) genotype and overweight/obesity in Mexican pediatric population.

摘要

背景

脑源性神经营养因子(BDNF)rs6265(G196A;Val66Met)单核苷酸多态性与不同人群的 BMI 和肥胖有关,包括成人和儿童,但涉及 Val 或 Met 作为风险变体的结果相互矛盾。

目的

确定 BDNF Val66Met 多态性与墨西哥儿童和青少年 BMI 之间的关联。

方法

通过 Fisher 精确检验关联分析,对儿科志愿者(n=498)的 BDNF Val66Met 基因分型和通过 BMI 年龄 z 评分(BAZ)描述的营养状况进行分析。使用标准化残差(R)来确定哪种基因型/等位基因对显著 Fisher 精确检验统计量有主要影响。使用比值比(OR)来衡量基因型与正常体重(≥-2 SD < +1 SD)和超重(≥+1 SD,包括肥胖,Ow+Ob)状态之间的关联,95%置信区间(CI)用于估计效应的精度,95%可信区间(CrI)用于获得最可能的估计值。

结果

GG(Val/Val)、GA(Val/Met)和 AA(Met/Met)基因型或 Met 纯合子与 Val 携带者(GG 和 GA 基因型的组合)之间的比较显示,正常体重和超重肥胖儿科患者之间存在显著差异(p=0.034 和 p=0.037)。我们的数据表明,与 Val 携带者相比,A 等位基因纯合子的儿童/青少年超重风险增加(贝叶斯 OR=4.2,95%CI**[1.09-33.1])。

结论

这是第一项表明 BDNF rs6265 AA(Met/Met)基因型与墨西哥儿科人群超重/肥胖之间存在显著关联的研究。

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