Huda Nafiul, Yasmin Tahirah, Nabi A H M Nurun
Laboratory of Population Genetics, Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh.
Laboratory of Population Genetics, Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh.
J Diabetes Complications. 2021 Oct;35(10):108018. doi: 10.1016/j.jdiacomp.2021.108018. Epub 2021 Aug 10.
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.
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.
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.
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.
2型糖尿病（T2D）是一种多因素疾病，会影响多个器官，并可能改变端粒酶（由hTERT基因编码）的活性，因此可能影响端粒长度。hTERT基因中串联重复序列MNS16A的可变数目通过调节端粒酶促进端粒的延长。在本研究中，对hTERT基因中MNS16A串联重复序列进行了基因分析，目的是找出等位基因和基因型变异与孟加拉人群T2D风险之间的任何关联。
本研究共纳入395例无亲缘关系的T2D患者和247例健康个体。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，使用逻辑回归分析等位基因和基因型频率与T2D风险的关联。进行哈迪-温伯格平衡（HWE）检验以评估基因型频率的一致性，并使用卡方检验检验与HWE的偏差。
逻辑回归分析显示，当将长等位基因（常见）作为对照时，含243 bp的短等位基因与T2D显著相关（OR：1.37，p = 0.03）。杂合基因型272/302与T2D风险降低显著相关（OR：0.33，p = 0.001）。基因型的综合结果表明，在显性模型下（LL与SL + SS相比；OR：2.62，p < 0.0001），MNS16A多态性与T2D风险增加显著相关。有趣的是，短等位基因243仅在男性人群中与疾病风险相关（OR：1.62，p = 0.02）。单独分析男性各自的数据时，基因型272/302也与T2D风险降低相关。
我们在孟加拉人群中鉴定出四个串联重复可变数目，它们与T2D的关联模式各不相同，为了扩展我们对这些VNTRs的理解，有必要进行进一步的大规模研究。
