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肥胖和非酒精性脂肪性肝病对白细胞端粒长度和端粒酶逆转录酶基因 MNS16A VNTR 变体的影响。

Effect of obesity and NAFLD on leukocyte telomere length and hTERT gene MNS16A VNTR variant.

机构信息

Department of Pediatrics, Istanbul Health and Technology University Faculty of Medicine, Istanbul, Turkey.

Adolescent Health PhD Program, Institute of Graduate Studies in Health Sciences, Istanbul University, Istanbul, Turkey.

出版信息

Sci Rep. 2024 Oct 23;14(1):25055. doi: 10.1038/s41598-024-77091-5.

Abstract

It is known that telomere length (TL) (evaluated with T/S ratio) is shortened in the presence of obesity. In this study, we aimed to investigate how obesity in adolescents and non-alcoholic liver disease (NAFLD) within the obese group affect TL and the clinical significance of the human telomerase reverse transcriptase (hTERT) gene MNS16A VNTR variant in terms of NAFLD. Adolescents with exogenous obesity and healthy controls (aged 10-19 years) who applied to our adolescent outpatient clinic between May-October 2023 were included in this study. We performed upper abdominal ultrasonography to investigate the presence of NAFLD in adolescents with obesity and divided into two groups: those without hepatosteatosis (obese NAFLD (-)) and those with hepatosteatosis (obese NAFLD (+)). We recorded body weight, height, waist circumference, and blood pressure measurements and measured the T/S ratio (telomere sequence copy number/gene single copy number) by the Quantitative Polymerase Chain Reaction method. The groups were compared using frequentist and Bayesian methods. Eighty-three obese adolescents [63 NAFLD(+) 20 NAFLD(-)] and 69 lean controls were included in the study. Pairwise comparisons revealed that T/S ratio was significantly lower in the obese NAFLD (-) group than the obese NAFLD (+) and the control group (p = 0.025, p = 0.007, respectively). T/S ratio was lower in the LL allele group than in the other alleles (p = 0.022) and slightly higher in the obese group with metabolic syndrome compared to the obese group without metabolic syndrome (p = 0.072). hTERT-MNS16A-VNTR gene variant LL allele had a negative correlation with T/S ratio among the obese adolescent group. Patients with LL alleles had higher ALT, GGT, HOMA-IR, and ALT/AST. Diastolic blood pressure had a significant correlation with the T/S ratio. The T/S ratio was shorter in the obese adolescent group compared to healthy ones but was higher in the NAFLD (+) obese compared to the NAFLD (-) obese. ALT level and ALT/AST ratio were higher, T/S ratio was lower in the hTERT MNS16A VNTR variant LL allele group among obese adolescents. In addition, there was a significant correlation between the T/S ratio and diastolic blood pressure in obese adolescents.

摘要

已知端粒长度(TL)(通过 T/S 比值评估)在肥胖存在的情况下会缩短。在这项研究中,我们旨在研究青少年肥胖和非酒精性脂肪性肝病(NAFLD)在肥胖组中如何影响 TL,以及人端粒酶逆转录酶(hTERT)基因 MNS16A VNTR 变体在 NAFLD 方面的临床意义。本研究纳入了 2023 年 5 月至 10 月期间在我院青少年门诊就诊的外源性肥胖青少年和健康对照组(年龄 10-19 岁)。我们对肥胖青少年进行上腹部超声检查,以调查是否存在 NAFLD,并将其分为两组:无肝脂肪变性(肥胖性非酒精性脂肪性肝病(-))和有肝脂肪变性(肥胖性非酒精性脂肪性肝病(+))。我们记录体重、身高、腰围和血压测量值,并通过定量聚合酶链反应方法测量 T/S 比值(端粒序列拷贝数/基因单拷贝数)。使用频率论和贝叶斯方法对各组进行比较。本研究纳入了 83 名肥胖青少年[63 名非酒精性脂肪性肝病(+),20 名非酒精性脂肪性肝病(-)]和 69 名瘦对照组。两两比较显示,肥胖性非酒精性脂肪性肝病(-)组的 T/S 比值明显低于肥胖性非酒精性脂肪性肝病(+)组和对照组(p=0.025,p=0.007)。LL 等位基因组的 T/S 比值低于其他等位基因(p=0.022),代谢综合征肥胖组的 T/S 比值略高于非代谢综合征肥胖组(p=0.072)。在肥胖青少年组中,hTERT-MNS16A-VNTR 基因变异 LL 等位基因与 T/S 比值呈负相关。LL 等位基因患者的 ALT、GGT、HOMA-IR 和 ALT/AST 更高。舒张压与 T/S 比值有显著相关性。与健康对照组相比,肥胖青少年组的 T/S 比值较短,但肥胖性非酒精性脂肪性肝病(+)组的 T/S 比值高于肥胖性非酒精性脂肪性肝病(-)组。肥胖青少年中 hTERT MNS16A VNTR 变体 LL 等位基因组的 ALT 水平和 ALT/AST 比值较高,T/S 比值较低。此外,肥胖青少年的 T/S 比值与舒张压之间存在显著相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f85/11499813/98aef140c41c/41598_2024_77091_Fig1_HTML.jpg

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