APOB基因3′端短串联重复序列多态性与新疆维吾尔族自然长寿的关系

Comparative study of APOB gene 3′VNTR polymorphisms between natural longevity and controls in Uighur nationality

目的探讨载脂蛋白B（apolipoprotein B，APOB）基因第29外显子3′端可变数目串联重复序列（variable number of tandem repeat, VNTR）多态性与维吾尔族自然长寿的关系。方法选择191名年龄90岁以上的健康个体为长寿组，另选53名年龄65～70岁、性别、地域相匹配已自然死亡的正常个体为对照组。应用序列特异引物PCR和PCR-直接测序等技术对APOB进行分型，并测定等位基因HVE36和HVE48的核苷酸序列。结果在维吾尔族人群（长寿组191名，对照组53名）中，共发现14个等位基因。长寿组中HVE36、HVE42频率显著高于对照组（P〈0．05），并且HVE44、HVE46、HVE48、HVE58仅见于长寿组，而HVE26、HVE30、HVE34显著低于对照组（P〈0．05）。逐步逻辑回归分析显示，L等位基因和LL基因型与年龄呈正相关，而S等位基因和SS基因型与年龄呈负相关（P〈0．05）。核苷酸序列分析显示，每一种等位基因由富含AT的15bp长的基本单位或它们的变异体串联重复而构成。结论APOB等位基因S和基因型SS可能是维吾尔族自然长寿老人的危险因素，而等位基因L和基因型LL则是其保护因子。

Objective To investigate the association of polymorphisms in the apolipoprotein B gene （APOB） 3＇ variable number of tandem repeat with natural longevity in the Xinjiang Uighur nationality people. Methods Totally 191 healthy individuals over 90 years and 53 individuals aged 65-70 years were recruited among Xinjiang Uighur population, the nationality, gender and living area were matched. Genotyping was performed using polymerase chain reaction-sequence specific primer（PCR-SSP） and PCR-sequencing. Results Fourteen alleles were found in the Xinjiang Uighur nationality population. The frequency of HVE36 and HVE42 in the natural longevity group were significantly higher than that in the control group （both P 〈 0.05） and HVE44, HVEA6, HVE48 and HVE58 were only found in the natural longevity group. However, the frequency of HVE26, HVE30 and HVE34 were markedly lower in the natural longevity group compared to the control group. Logistic regression analyses revealed that allele L and the genotypes LL were positively associated with age, whereas the allele S and genotype SS were negatively associated with age （ both P 〈 0.05）. Each allele consists of 15 bp tandem repeats with rich-AT by PCR-sequencing. Conclusion These results indicate that the S allele, and SS genotype are frail factors in China Uighur natural longevity people, whereas allele L and genotypes LL are protective factors.