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Genetic susceptibility to telomere shortening through the rs2293607 polymorphism is associated with a greater risk of alcohol use disorder
Mechanisms of Ageing and Development ( IF 5.3 ) Pub Date : 2022-06-26 , DOI: 10.1016/j.mad.2022.111693
Hernán Llorente 1 , Jose-Angel Perez-Rivera 2 , María Perez-Nieto 3 , Clara Cieza-Borrella 4 , Isabel Pastor 5 , Ignacio Novo-Veleiro 6 , Javier Fernández-Mateos 7 , Antonio-Javier Chamorro 1 , Patricia Crecente-Otero 8 , Francisco-Javier Laso 1 , Rogelio González-Sarmiento 7 , Miguel Marcos 5
Affiliation  

Telomere shortening is usually considered a biomarker of ageing. Harmful alcohol use promotes accelerated biological ageing and alcohol use disorders (AUDs) are associated with short telomere length (TL). This study was conducted to examine the relationship of TL to AUD and determine whether single nucleotide polymorphisms (SNPs) in TERC and TERT modulate this association. For this purpose, we genotyped TERC SNPs rs2293607, rs12696304, and rs16847897 and TERT SNPs rs2735940, rs2736100, and rs2736098 in 308 male patients with AUD and 255 sex-matched healthy controls and measured TL in a subset of 99 patients and 99 controls paired by age and smoking status. Our results showed that the mean TL was shorter in patients with AUD than in controls. The area under the ROC curve was 0.70 (P < 0.001). The GG genotype of TERC rs2293607 was more common among patients with AUD than among controls (9.8% vs. 5.1%; P = 0.038). No difference was found for the other SNPs. Carriers of the GG genotype of rs2293607 had shorter telomeres than did allele A carriers. In conclusion, patients with AUD had shorter telomeres. Genetic susceptibility to telomere shortening through the rs2293607 SNP is associated with a greater risk of AUD.



中文翻译:

通过 rs2293607 多态性对端粒缩短的遗传易感性与更大的酒精使用障碍风险相关

端粒缩短通常被认为是衰老的生物标志物。有害的酒精使用会加速生物老化,酒精使用障碍 (AUD) 与端粒长度 (TL) 短有关。本研究旨在检查 TL 与 AUD 的关系,并确定TERCTERT中的单核苷酸多态性 (SNP) 是否调节这种关联。为此,我们对TERC SNP rs2293607、rs12696304 和 rs16847897 和TERT进行基因分型SNP rs2735940、rs2736100 和 rs2736098 在 308 名 AUD 男性患者和 255 名性别匹配的健康对照中,并在 99 名患者和 99 名对照中按年龄和吸烟状况配对测量 TL。我们的结果表明,AUD 患者的平均 TL 比对照组短。ROC曲线下面积为0.70(P  <0.001)。TERC rs2293607的 GG 基因型在 AUD 患者中比在对照组中更常见(9.8% 对 5.1%;P  = 0.038)。其他 SNP 没有发现差异。rs2293607 GG 基因型的携带者比等位基因A 携带者具有更短的端粒。总之,AUD 患者的端粒较短。通过 rs2293607 SNP 对端粒缩短的遗传易感性与更大的 AUD 风险相关。

更新日期:2022-06-29
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