Panigrahi Rajesh, Sarkar Neelakshi, Biswas Avik, Pal Ananya, Saha Debraj, Singh Shivaram P, Panigrahi Manas K, Bandopadhyay Manikanana, Chakrabarti Sekhar, Chakravarty Runu
ICMR Virus Unit Kolkata, ID and BG Hospital Campus, GB4, 1st Floor, 57 Dr S.C. Banerjee Road, Kolkata 700012, West Bengal, India.
Department of Gastroenterology, SCB Medical College, Cuttack, Orissa, India ; Kalinga Gastroenterology Foundation, Bajrakabati Road, Cuttack, Orissa, India.
J Clin Exp Hepatol. 2014 Sep;4(3):202-8. doi: 10.1016/j.jceh.2014.08.002. Epub 2014 Sep 18.
TNF-α promoter polymorphism has been known to be a potential predictive factor in patients with HBV infection. We therefore tried to investigate whether the TNF-α promoter polymorphism at position -238, -857 and -863 was associated with the outcome of HBV infection in a population from Orissa, southern part of East India.
A total of 195 patients recruited for the study were classified into 85 controls and 110 HBV infected cases, which included 34 IC, 30 CLD, 32 LC and 14 HCC patients. The polymorphisms at the respective sites were detected by a PCR-RFLP followed by statistical analysis.
The frequency of the genotype -238 GG and the allele -238G in the cases (89.0% and 92.7% respectively) was significantly higher than that in the controls (68.2% and 82.2% respectively) (P < 0.001, OR = 3.8 and P = 0.001, OR = 2.73). Whereas the -238 GA genotype was significantly high in the control group (28.2%) when compared to the cases (7.2%) (P < 0.001, OR = 0.2). Similarly, the frequency of -863CC and the allele -863C was significantly higher among the cases (24.5% and 49.5%) compared to controls (1.17% and 34.7%), (P < 0.001, OR = 27.32 and P = 0.003, OR = 1.85), whereas the -863CA genotype was significantly high in the controls (67.0%) when compared to the cases (50.0%) (P = 0.01, OR = 0.49). Haplotype -863C/-857C/-238G in cases was significantly higher than controls (P = 0.002). Multivariate logistic regression analysis indicates that the genotype -863CC bears a negative association with liver disease progression.
The present study established an association of polymorphisms at site -238 and -863 of the TNF-α promoter with the outcome HBV infection and disease progression.
已知肿瘤坏死因子-α(TNF-α)启动子多态性是乙肝病毒(HBV)感染患者的一个潜在预测因素。因此,我们试图调查位于-238、-857和-863位点的TNF-α启动子多态性是否与印度东部南部奥里萨邦人群的HBV感染结局相关。
本研究共招募了195名患者,分为85名对照组和110名HBV感染病例组,其中包括34例慢性炎症(IC)、30例肝硬化(CLD)、32例肝衰竭(LC)和14例肝癌(HCC)患者。通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测各位点的多态性,随后进行统计分析。
病例组中-238GG基因型和-238G等位基因的频率(分别为89.0%和92.7%)显著高于对照组(分别为68.2%和82.2%)(P<0.001,比值比[OR]=3.8;P=0.001,OR=2.73)。而-238GA基因型在对照组中(28.2%)显著高于病例组(7.2%)(P<0.001,OR=0.2)。同样,-863CC基因型和-863C等位基因在病例组中的频率(分别为24.5%和49.5%)显著高于对照组(分别为1.17%和34.7%)(P<0.001,OR=27.32;P=0.003,OR=1.85),而-863CA基因型在对照组中(67.0%)显著高于病例组(50.0%)(P=0.01,OR=0.49)。病例组中-863C/-857C/-238G单倍型显著高于对照组(P=0.002)。多因素逻辑回归分析表明,-863CC基因型与肝病进展呈负相关。
本研究证实了TNF-α启动子-238和-863位点的多态性与HBV感染结局及疾病进展之间存在关联。