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与库尔德人群 COVID-19 易感性和死亡率相关的人口统计学、临床和遗传因素。

Demographic, clinical and genetic factors associated with COVID-19 disease susceptibility and mortality in a Kurdish population.

机构信息

From the Department of Biology, College of Science, Salahaddin University-Erbil, Iraq.

From the Department of Biology, School of Natural Sciences, University of Tabriz, Tabriz, Iran.

出版信息

Ann Saudi Med. 2023 May-Jun;43(3):125-142. doi: 10.5144/0256-4947.2023.125. Epub 2023 Jun 1.

DOI:10.5144/0256-4947.2023.125
PMID:37270678
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10317494/
Abstract

BACKGROUND

Coronavirus disease 2019 (COVID-19) is a devastating pandemic that causes disease with a variability in susceptibility and mortality based on variants of various clinical and demographic factors, including particular genes among populations.

OBJECTIVES

Determine associations of demographic, clinical, laboratory, and single nucleotide polymorphisms in the -α, and -γ genes to the incidence of infection and mortality in COVID-19 patients.

DESIGN

Prospective cohort study SETTINGS: Various cities in the Kurdistan Region of Iraq.

PATIENTS AND METHODS

This prospective cohort study compared laboratory markers (D-dimer, tumor necrosis factor-alpha [TNF-α], interferon-gamma [IFN-γ], C-reactive protein [CRP], lymphocyte and neutrophil counts) between COVID-19 patients and healthy controls. DNA was extracted from blood, and genotypes were done by Sanger sequencing.

MAIN OUTCOME MEASURES

Single nucleotide polymorphisms of the -α, and -γ genes and demographic characteristics and laboratory markers for predicting mortality in COVID-19.

SAMPLE SIZE

203 (153 COVID-19 patients, 50 health control subjects).

RESULTS

Forty-eight (31.4%) of the COVID-19 patients died. Age over 40 and comorbidities were risk factors for mortality, but the strongest associations were with serum IFN-γ, the neutrophil-to-lymphocyte ratio (NLR), and serum TNF-α. The AA genotype and A allele of rs2070788 decreased while the GA genotype and A allele of -α increased susceptibility to COVID-19. Patients with the GA genotype of TNF-α rs1800629 had shorter survival times (9.9 days) than those carrying the GG genotype (18.3 days) (<.0001 by log-rank test). The GA genotype versus the GG genotype was associated with higher levels of serum TNF-α. The GA genotype increased mortality rates by up to 3.8 fold. The survival rate for COVID-19 patients carrying the -γ rs2430561 TT genotype (58.5%) was lower than in patients with the TA and AA genotypes (80.3%). The TT genotype increased the risk of death (HR=3.664, <.0001) and was linked to high serum IFN-γ production. Olfactory dysfunction was a predictor of survival among COVID-19 patients.

CONCLUSIONS

Age older than 40, comorbidities, the NLR and particular genotypes for and the -γ and -α genes were risk factors for death. Larger studies in different populations must be conducted to validate the possible role of particular SNPs as genetic markers for disease severity and mortality in COVID-19 disease.

LIMITATIONS

Small sample size.

CONFLICT OF INTEREST

None.

摘要

背景

2019 年冠状病毒病(COVID-19)是一种具有破坏性的大流行病,它会导致疾病,其易感性和死亡率因各种临床和人口统计学因素的变异而有所不同,包括人群中的特定基因。

目的

确定-α和-γ基因中的人口统计学、临床、实验室和单核苷酸多态性与 COVID-19 患者感染和死亡率的关系。

设计

前瞻性队列研究

地点

伊拉克库尔德地区的各个城市。

患者和方法

这项前瞻性队列研究比较了 COVID-19 患者和健康对照组之间的实验室标志物(D-二聚体、肿瘤坏死因子-α[TNF-α]、干扰素-γ[IFN-γ]、C 反应蛋白[CRP]、淋巴细胞和中性粒细胞计数)。从血液中提取 DNA,并通过 Sanger 测序进行基因分型。

主要观察指标

-α和-γ基因的单核苷酸多态性以及人口统计学特征和实验室标志物,用于预测 COVID-19 患者的死亡率。

样本量

203 例(153 例 COVID-19 患者,50 例健康对照)。

结果

COVID-19 患者中有 48 例(31.4%)死亡。年龄超过 40 岁和合并症是死亡的危险因素,但与死亡率最密切相关的是血清 IFN-γ、中性粒细胞与淋巴细胞比值(NLR)和血清 TNF-α。rs2070788 的 AA 基因型和 A 等位基因减少,而-α的 GA 基因型和 A 等位基因增加了 COVID-19 的易感性。TNF-αrs1800629 的 GA 基因型患者的生存时间(9.9 天)短于 GG 基因型患者(18.3 天)(对数秩检验<.0001)。GA 基因型与较高的血清 TNF-α水平相关。GA 基因型使死亡率增加了 3.8 倍。携带-γrs2430561 TT 基因型的 COVID-19 患者的存活率(58.5%)低于 TA 和 AA 基因型患者(80.3%)。TT 基因型增加了死亡风险(HR=3.664,<.0001),与高血清 IFN-γ产生有关。嗅觉功能障碍是 COVID-19 患者生存的预测指标。

结论

年龄大于 40 岁、合并症、NLR 以及-α和-γ基因的特定基因型是死亡的危险因素。必须在不同人群中进行更大规模的研究,以验证特定 SNPs 作为 COVID-19 疾病严重程度和死亡率的遗传标志物的可能作用。

局限性

样本量小。

利益冲突

无。

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