BDNF Val66Met多态性与长寿群体代谢综合征危险因素的相关性研究

Val66Met polymorphism of BDNF gene and its association with risk factors of metabolic syndrome in long-living population

目的 探讨广西地区长寿人群脑源性神经营养因子（BDNF）Val66Met的多态性与代谢综合征危险因素（BMI、血糖、血脂水平、血压水平等）的相关性。方法 用扩增受阻突变体系聚合酶链式反应技术（ARMS-PCR）对广西红水河流域壮族长寿老人487例（长寿组）、长寿老人的子女593例（子女组）及普通健康中老年人582例（对照组）进行BDNF Val66Met的基因分型,并分析各基因型与代谢综合征危险因素的相关性。结果 长寿组、子女组及对照组BDNF Val66Met位点最小等位基因（A）频率分别为44.3%、41.1%及41.9%,等位基因及基因型频率分布在三组间无明显差异（P均〉0.05）,且不受性别的影响;而组内比较显示对照组女性AA基因型的频率高于男性（20.9%vs 14.6%,P=0.004）。整体人群及对照组A基因型携带者（GA/AA）的HDL-C水平低于非A基因型携带者（GG）（F=6.904,P=0.009;F=7.616,P=0.006）;按性别、BMI、血糖、血脂水平分层后,此种趋势在对照组的女性、高血糖亚组、血脂正常亚组依然存在;而且对照组A基因型发生超重的风险是非A基因型的1.63倍（OR=1.63,95%CI：1.05~2.55）,其收缩压水平也高于非A基因型携带者;对照组血脂正常亚组的A基因型的BMI、TG水平高于非A携带者。多元线性回归分析发现长寿组的TC水平与BDNF Val66Met基因型存在负相关。结论 BDNF 66Met可降低广西地区普通中老年人群的HDL-C水平并有导致超重的风险,而对长寿老人及其子女影响不大。

Objective To evaluate the association of the Val66Met polymorphism （rs6265） of brain-derived neurotrophic factor （BDNF） gene with the risk factors of metabolic syndrome, such as BMI, plasma glucose and lipid levels and blood pressure, in long- living population of Guangxi region. Methods Genetyping the BDNF Va166Met polymorphism was performed by amplified refractory mutation system（ARMS）-PCR in 487 long-living individuals （long-living group, LG）, 593 offspring of the long-living individuals （offspring group, OG） and 582 healthy middle and aged persons（ control group, CG）. Then, the correlation between the genotypes and risk factors of metabolic syndrome was analyzed. Results The minor allele frequencies（ allele A） of BDNF rs6265 in LG, OG and CG groups were 44.3%, 41.1% and 41.9%, respectively, without any significant difference between them（P 〉 0.05）. However, the frequency of AA genotype in the females of CG group was significantly higher than that in the males（20.9% vs 14.6%, P =0. 004）. The HDL-C levels in the genotype A（GA/AA） carriers were significantly lower than that in the genotype non-A（GG） carriers in both control group （ F = 7. 616, P = 0.006） and all participants （ F = 6. 904, P = 0. 009）. Dichotomized analyses for sex, BMI, and serum glucose and lipid levels, the HDL-C levels in the genotype A （GA/AA） carriers of the GC females, hyperglycemic subgroup and normolipidemic subgroup were also significantly lower than that in the genotype non-A（GG） carriers. Moreover, the overweight risk in the genotype A carriers of CG was 1.63 times of the genotype non-A carriers（ OR = 1.63, 95% CI ： 1.05-2.55）, and the systolic blood pressure in the former was also higher than that in the latter. The BMI and serum TG levels in the genotype A carriers of CG with ortholiposis were higher than that in the genotype non-A carriers. Multiple linear regression analysis showed that the serum TC level in LG was negatively related to the Va166Met genotype of BDNF gene. Conclusion BDNF 66Met may reduce the serum HDL-C level and lead to the overweight of general population in Guangxi region, but has less impact on the long-living individuals and their offspring.