端粒相关基因的相对白细胞端粒长度和遗传变异与血清水平在年龄相关性黄斑变性中的作用。

Relative Leukocyte Telomere Length and Genetic Variants in Telomere-Related Genes and Serum Levels Role in Age-Related Macular Degeneration.

机构信息

Laboratory of Ophthalmology, Neuroscience Institute, Medical Academy, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania.

Department of Ophthalmology, Medical Academy, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania.

出版信息

Cells. 2022 Nov 30;11(23):3847. doi: 10.3390/cells11233847.

DOI:10.3390/cells11233847

PMID:36497103

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9740443/

Abstract

UNLABELLED

Telomere shortening is well known to be associated with ageing. Age is the most decisive risk factor for age-related macular degeneration (AMD) development. The older the individual, the higher the AMD risk. For this reason, we aimed to find any associations between telomere length, distribution of genetic variants in telomere-related genes (, , , , and ), and serum TERF-1 and TERF2 levels on AMD development.

METHODS

Our study enrolled 342 patients with AMD and 177 healthy controls. Samples of DNA from peripheral blood leukocytes were extracted by DNA salting-out method. The genotyping of rs2736098, rs401681 in locus, rs1545827, rs10107605, rs10509637, rs10509639, and rs251796 and relative leukocyte telomere length (T/S) measurement were carried out using the real-time polymerase chain reaction method. Serum TERF-1 and TERF2 levels were measured by enzymatic immunoassay (ELISA).

RESULTS

We found longer telomeres in early AMD patients compared to the control group. Additionally, we revealed that minor allele C at rs10107605 was associated with decreases the odds of both early and exudative AMD. Each minor allele G at rs251796 and rs1545827 C/T genotype and C/T+T/T genotypes, compared to the C/C genotype, increases the odds of having shorter telomeres. Furthermore, we found elevated TERF1 serum levels in the early AMD group compared to the control group.

CONCLUSIONS

In conclusion, these results suggest that relative leukocyte telomere length and genetic variants of and play a role in AMD development. Additionally, TERF1 is likely to be associated with early AMD.

摘要

目的

端粒缩短与衰老密切相关。年龄是年龄相关性黄斑变性（AMD）发展的最决定性风险因素。个体年龄越大，AMD 的风险越高。因此，我们旨在寻找端粒长度、端粒相关基因（、、、、和）中遗传变异的分布以及 AMD 发展过程中端粒体相关因子 1（TERF-1）和 TERF-2 血清水平之间的任何关联。

方法

本研究纳入了 342 名 AMD 患者和 177 名健康对照者。采用 DNA 盐析法提取外周血白细胞 DNA。采用实时聚合酶链反应法对 rs2736098、位点 rs401681、rs1545827、rs10107605、rs10509637、rs10509639 和 rs251796 的基因分型及相对白细胞端粒长度（T/S）进行测量。采用酶联免疫吸附法（ELISA）检测血清 TERF-1 和 TERF2 水平。

结果

与对照组相比，早期 AMD 患者的端粒较长。此外，我们发现 rs10107605 中的次要等位基因 C 与早期和渗出性 AMD 的几率降低有关。与 C/C 基因型相比，rs251796 和 rs1545827 的每个次要等位基因 G 和 C/T+T/T 基因型均增加了端粒较短的几率。此外，我们发现早期 AMD 组的 TERF1 血清水平高于对照组。