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Association of polymorphisms in TNF-α, IL-1β, GSTM and GSTT genes with apical periodontitis: is there a link with herpesviral infection?
International Endodontic Journal ( IF 5 ) Pub Date : 2020-04-20 , DOI: 10.1111/iej.13298
A Jakovljevic 1 , N Nikolic 2 , J Carkic 2 , K Beljic-Ivanovic 3 , I Soldatovic 4 , M Miletic 1 , M Andric 5 , J Milasin 2
Affiliation  

AIM To investigate the possible association between TNFα (-308 G/A) and IL-1β (-511 C/T) single nucleotide polymorphisms (SNPs) and GSTT and GSTM deletion polymorphisms and risk of apical periodontitis (AP) development, and determine the association of different genotypes with the presence of herpesviral infection in AP. METHODOLOGY The study included 120 periapical lesions and 200 control samples. Gene polymorphism analysis was performed using either polymerase chain reaction (PCR) or PCR/ restriction fragment length polymorphism (RFLP). Relative gene expression of TNF-α and IL-1β was analysed using reverse transcriptase - real-time PCR. The presence of Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) was assessed by nested PCR. Chi-square and Fisher's exact tests and logistic regression analyses were done for polymorphisms, whilst Mann-Whitney U-test was performed for the expression analysis. The expected frequency of variants was analysed by the Hardy-Weinberg equilibrium test. RESULTS TNF-α (-308 G/A) SNP increased AP susceptibility for heterozygous (odds ratio (OR) = 1.72, 95% confidence interval (CI) = 1.06-2.80, P = 0.027) and homozygous (OR = 8.55, 95% CI = 1.77-41.36, P < 0.001) carriers of the variant A allele. On the other hand, IL-1β (-511 C/T) polymorphism exerted a protective effect both in heterozygotes (OR = 0.540, 95% CI = 0.332-0.880, P = 0.013) and homozygotes (OR = 0.114, 95% CI = 0.026-0.501, P < 0.001). In addition, GSTM1 and GSTT1 null genotypes separately, as well as concomitantly, were associated with an increased risk for AP development (P < 0.001). The null GSTT1 genotype increased approximately twice the risk of Epstein-Barr infection (EBV) in AP (OR = 2.17, 95% CI = 1-4.71, P = 0.048), whilst TNF-α SNP decreased it, both in heterozygotes (OR = 0.20, 95% CI = 0.08-0.48, P < 0.001) and AA homozygotes (OR = 0.07, 95% CI = 0.01-0.37, P = 0.001). CONCLUSIONS GSTM and GSTT deletion polymorphisms, as well as TNFα (-308 G/A) SNP, are associated with increased risk, whereas IL-1β (-511 C/T) polymorphism decreases the risk of AP development. GSTT and TNFα polymorphisms also appear to modulate the risk of EBV infection in Serbian patients with AP.

中文翻译:

TNF-α、IL-1β、GSTM 和 GSTT 基因多态性与根尖周炎的相关性:与疱疹病毒感染有联系吗?

目的 探讨 TNFα (-308 G/A) 和 IL-1β (-511 C/T) 单核苷酸多态性 (SNPs) 和 GSTT 和 GSTM 缺失多态性与根尖周炎 (AP) 发展风险之间的可能关联,并确定不同基因型与 AP 中存在疱疹病毒感染的关联。方法 该研究包括 120 个根尖周病变和 200 个对照样本。使用聚合酶链式反应(PCR)或PCR/限制性片段长度多态性(RFLP)进行基因多态性分析。使用逆转录酶-实时PCR分析TNF-α和IL-1β的相对基因表达。通过巢式 PCR 评估 Epstein-Barr 病毒 (EBV) 和人类巨细胞病毒 (HCMV) 的存在。对多态性进行卡方和Fisher精确检验和逻辑回归分析,而 Mann-Whitney U-test 用于表达分析。通过 Hardy-Weinberg 平衡检验分析变体的预期频率。结果 TNF-α (-308 G/A) SNP 增加了杂合子(优势比 (OR) = 1.72, 95% 置信区间 (CI) = 1.06-2.80, P = 0.027)和纯合子 (OR = 8.55, 95) 的 AP 易感性% CI = 1.77-41.36, P < 0.001) 变异 A 等位基因的携带者。另一方面,IL-1β(-511 C/T)多态性在杂合子(OR = 0.540, 95% CI = 0.332-0.880, P = 0.013)和纯合子(OR = 0.114, 95% CI = 0.026-0.501,P < 0.001)。此外,GSTM1 和 GSTT1 无效基因型分别以及同时与 AP 发展风险增加相关(P < 0.001)。无 GSTT1 基因型使 AP 中 Epstein-Barr 感染 (EBV) 的风险增加了大约两倍(OR = 2.17, 95% CI = 1-4.71, P = 0.048),而 TNF-α SNP 降低了它,无论是在杂合子中(OR = 0.20, 95% CI = 0.08-0.48, P < 0.001) 和 AA 纯合子 (OR = 0.07, 95% CI = 0.01-0.37, P = 0.001)。结论 GSTM 和 GSTT 缺失多态性以及 TNFα (-308 G/A) SNP 与风险增加有关,而 IL-1β (-511 C/T) 多态性降低 AP 发展的风险。GSTT 和 TNFα 多态性似乎也可以调节塞尔维亚 AP 患者感染 EBV 的风险。结论 GSTM 和 GSTT 缺失多态性以及 TNFα (-308 G/A) SNP 与风险增加有关,而 IL-1β (-511 C/T) 多态性降低 AP 发展的风险。GSTT 和 TNFα 多态性似乎也可以调节塞尔维亚 AP 患者感染 EBV 的风险。结论 GSTM 和 GSTT 缺失多态性以及 TNFα (-308 G/A) SNP 与风险增加有关,而 IL-1β (-511 C/T) 多态性降低 AP 发展的风险。GSTT 和 TNFα 多态性似乎也可以调节塞尔维亚 AP 患者感染 EBV 的风险。
更新日期:2020-03-26
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