Background

Type 2 diabetes (T2D) is a multifactorial disorder that affects multi-organ and can alter telomerase (encoded by hTERT gene) activity and thus, may affect telomere length. The variable number of tandem repeats MNS16A in hTERT gene facilitates extension of telomeres by regulating telomerase. In the present study, genetic analysis of MNS16A tandem repeats in hTERT gene was performed with the aim of finding out any association of allelic and genotypic variations with the risk of T2D in Bangladeshi population.

Methods

A total of unrelated 395 individuals with T2D and 247 healthy individuals were included in the study. The genotypic and allelic frequencies were determined using allele specific polymerase chain reaction. The association of allelic and genotypic frequencies with risk of T2D was analyzed using logistic regression analysis on the basis of odds ratio at 95% confidence interval. Hardy-Weinberg equilibrium (HWE) test was performed to evaluate the uniformity of the genotypic frequencies and deviation from the HWE was tested using Chi-square test.

Results

Logistic regression analyses revealed significant association of short allele containing 243 bp (OR: 1.37 and p = 0.03) with T2D, when the long alleles (commonly found) were considered as reference. The heterozygous genotype 272/302 was significantly associated with the decreased risk of T2D (OR: 0.33, p = 0.001). The combined results of genotypes indicated that the MNS16A polymorphism was significantly associated with the increased risk of T2D under the dominant model (LL vs SL + SS; OR: 2.62, p < 0.0001). Interestingly, short allele 243 was associated with the risk of disease only in male population (OR: 1.62, p = 0.02). The genotype 272/302 was also found to be associated with the decreased risk of T2D when respective data for male was analyzed individually.

Conclusions

We have identified four variable number of tandem repeats with varying patterns of association with T2D in Bangladeshi population and to extend our knowledge of understanding regarding these VNTRs, further large-scale studies are warranted.

中文翻译：

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人类端粒酶基因的 MNS16A VNTR 多态性：阐明孟加拉国人群中与 2 型糖尿病相关的性别特异性潜在等位基因

背景

2 型糖尿病 (T2D) 是一种影响多器官的多因素疾病，可改变端粒酶（由hTERT基因编码）活性，因此可能影响端粒长度。hTERT基因中可变数量的串联重复MNS16A通过调节端粒酶促进端粒的延伸。在本研究中，对hTERT基因中的 MNS16A 串联重复序列进行了遗传分析，目的是找出等位基因和基因型变异与孟加拉国人群 T2D 风险的任何关联。

方法

共有 395 名不相关的 T2D 个体和 247 名健康个体被纳入研究。使用等位基因特异性聚合酶链反应确定基因型和等位基因频率。基于 95% 置信区间的优势比，使用逻辑回归分析分析等位基因和基因型频率与 T2D 风险的关联。进行 Hardy-Weinberg 平衡 (HWE) 测试以评估基因型频率的均匀性，并使用卡方检验测试与 HWE 的偏差。

结果

逻辑回归分析显示，当长等位基因（常见）被视为参考时，包含 243 bp（OR：1.37 和 p = 0.03）的短等位基因与 T2D 显着相关。杂合基因型 272/302 与 T2D 风险降低显着相关（OR：0.33，p = 0.001）。基因型的综合结果表明，在显性模型下，MNS16A 多态性与 T2D 风险增加显着相关（LL vs SL + SS；OR：2.62，p < 0.0001）。有趣的是，短等位基因 243 仅与男性人群的疾病风险相关（OR：1.62，p = 0.02）。当单独分析男性的相应数据时，还发现基因型 272/302 与 T2D 风险降低有关。

结论

我们已经确定了四个可变数量的串联重复序列，它们与孟加拉国人群中的 T2D 具有不同的关联模式，并且为了扩展我们对这些 VNTR 的理解知识，有必要进行进一步的大规模研究。