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    端粒相关基因多态性对长寿人群血糖水平的影响

    Influence of telomere-related gene polymorphisms on blood glucose levels in long-lived population

      摘要
    • 摘要:
      目的 探讨与端粒相关单核苷酸多态性（SNP）TERC rs12696304、MYNN rs3772190和LRRC31 rs16847897与广西巴马地区长寿人群血糖水平的相关性。
      方法 根据空腹血糖水平将纳入分析的284例90岁以上的长寿老人分为高血糖组（59例）和正常血糖组（225例）。采用TaqMan MGB探针法对3个SNP进行基因分型。用卡方检验和非条件性logistic回归分析评估SNP位点各基因型及等位基因频率在两组人群中的分布以及与血糖水平的关系。通过Haploview 4.2软件分析各位点间的连锁不平衡（LD），构建单倍体以了解基因间的交互情况。用广义多因子降维分析方法（GMDR）进一步分析基因—环境的交互作用对血糖水平异常的影响。
      结果 TERC rs12696304和MYNN rs3772190的基因型和等位基因频率分布在高血糖组和正常血糖组比较，差异有统计学意义（P＜0.05），LRRC31 rs16847897的等位基因在两组间分布比较，差异有统计学意义（P＜0.05），而基因型分布差异无统计学意义（P=0.06）；TERC rs12696304、MYNN rs3772190和LRRC31 rs16847897均与高血糖的风险相关；rs12696304、rs3772190和rs16847897 3个位点之间处于较强LD状态。单倍体G-A-C、C-G-G在两组间分布比较，差异有统计学意义（P＜0.05）；rs12696304与腰围（WC）之间存在SNP—环境相互作用（P=0.010 7）；C-G-G、C-G-C、TG和WC之间存在单倍体—环境相互作用（P=0.010 7）。
      结论 与端粒相关的SNP rs12696304、rs3772190和rs16847897与长寿人群的空腹血糖水平升高相关，SNP、单倍体与环境之间的不同交互作用方式对血糖升高风险表现出不同的效应。

       

      Abstract:
      Objectives To explore the correlation between the telomere-related single nucleotide polymorphisms (SNPs) in TERC rs12696304, MYNN rs3772190 and LRRC31 rs16847897 and blood glucose levels in the longlived population in Bama region of Guangxi.
      Methods According to the fasting blood glucose levels, 284 longlived elderly people over 90 years old included in the analysis were divided into hyperglycemia group (59 cases) and normoglycemia group (225 cases). The TaqManMGB probe method was used to genotype the three mentioned SNPs. Chi-square test and unconditional logistic regression analysis were used to evaluate the distributions of SNP genotypes and allele frequencies in the two groups as well as their relationships with blood glucose levels. Haploview 4.2 software was used to analyze the linkage disequilibrium (LD) between each locus, and haplotypes were constructed to understand the interaction between genes. The generalized multifactor dimensionality reduction (GMDR) was used to further analyze the influence of gene-environment interaction on abnormal blood glucose levels.
      Results There were statistically significant differences in the genotype and allele frequency distributions of TERC rs12696304 and MYNN rs3772190 between the hyperglycemia group and the normoglycemia group (P < 0.05). For LRRC31 rs16847897, there was a statistically significant difference in the allele distributions between the two groups (P < 0.05), while there was no statistically significant difference in the genotype distribution (P=0.06). TERC rs12696304, MYNN rs3772190 and LRRC31 rs16847897 were all associated with the risk of hyperglycemia. The three loci of rs12696304, rs3772190, and rs16847897 were in a strong state of linkage disequilibrium. The distributions of haplotypes G-A-C and C-G-G were significantly different between the two groups (P < 0.05). There was an SNP-environment interaction between rs12696304 SNP and waist circumference (WC) (P=0.0107). The haplotype-environment interaction existed among C-G-G, C-G-C, TG and WC (P=0.0107).
      Conclusion The telomere-related SNPs rs12696304, rs3772190 and rs16847897 are associated with el‐ evated fasting blood glucose levels in the long-lived population. Different interactions between SNPs, haplotypes, and the environment exhibit different effects on the risk of elevated blood glucose.

       

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