Effect of IL-12B, IL-2, TGF-β1, and IL-4 Polymorphism and Expression on Hepatitis B Progression

Abstract

The hepatitis B virus (HBV) infection-induced chronic inflammation is considered to be the major etiological factor for HBV-related disease chronicity. Cytokines act as the key coordinators of the inflammatory responses involved in HBV disease pathogenesis. The present study assessed association among IL-12B(+1188), IL-2(-330), TGF-β1(-509), and IL-4(-590) genotypes; mRNA; and protein levels with HBV-hepatocellular carcinoma (HCC) risk in India. For this, 403 subjects (153 controls, 67 inactive HBV-carriers, 62 chronic-active HBV patients, 62 HBV-cirrhotics, and 59 HBV-HCC ssubjects) were enrolled in the study. The genotyping was carried by polymerase chain reaction (PCR)-restriction fragment length polymorphism (IL-12+1188A/C, IL-2-330T/G, and TGF-β1-509C/T), and allele specific (AS)-polymerase chain reaction (IL-4-590C/T). Enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction methods were used for assessing protein and the mRNA expression, respectively, of the mentioned cytokines. The study revealed that the IL-12B(+1188) CC genotype shared a significant positive association with hepatitis, among controls. While, in the case of IL-2(-330), both the TG and GG genotypes were not significantly associated with HCC risk. The TGF-β1(-509) TT genotype acted as a potential protective factor for cirrhosis and the HCC risk, among carriers. On the contrary, the IL-4(-590) CT genotype was found to be a vital protective factor for the development of hepatitis, among carriers. Besides, IL-12B, TGF-β1, and IL-2 seem to be majorly involved in the development of HCC, while, IL-4 might be responsible for the progression of the HBV disease till cirrhosis development. These initial findings are indicative of the vital role of genotypes and/or levels of IL-12B, IL-2, IL-4, and TGF-β1 in HBV disease chronicity in Indian population.

Association between transforming growth factor-β1 -509 C>T variants and hepatocellular carcinoma susceptibility: a meta-analysis

“…There were 1,427 HCC cases and 3,735 controls, and all studies were hospital-based. In studies by Falleti et al [14], Qi et al [15], Radwan et al [16], Xin et al [17], and Shi et al [18], the control genotype distributions were in Hardy-Weinberg equilibrium, but they were not in the studies by Saxena et al [19] and Ma et al [20]. In the Kim et al study [13], it could not be determined whether the genotype distribution of the controls was in Hardy-Weinberg equilibrium because the TT and CT genotypes were counted as a single group.…”

“…Although most previous meta-analyses have reported negative results for this association, the results of primary studies seem to suggest some tendencies, in terms of the infecting hepatitis virus. Of the four studies including HBV-infected subjects, three indicated a significant association between TGF-β1 C-509T variants and decreased HCC susceptibility [13,15,17,19]. However, two studies using HCV-infected subjects suggested a significant association between TGF-β1 C-509T variants and increased HCC susceptibility [16,20].…”

“…Some studies have also described TGF-β1 gene variants in codons 10 and 25 of exon 1 and at the promoter region positions -800 and -509 [11,12]. Among these variants, TGF-β1 -509 C>T variants (rs1800469) have been most frequently examined as a possible genetic factor contributing to HCC susceptibility [13][14][15][16][17][18][19][20][21]. However, these studies have yielded conflicting results.…”

Single-nucleotide polymorphisms of the <i>IL-12</i> gene lead to a higher cancer risk: a meta-analysis based on 22,670 subjects

“…Among the remaining 69 articles, 31 studies, containing 10749 cancer patients and 11921 control subjects, were finally included in the present meta-analysis (Howell, et al, 2003;Amirzargar, et al, 2005;García-González, et al, 2007;Hou, et al, 2007;Lee, et al, 2007;Crusius, et al, 2008;Han, et al, 2008;Chen, et al, 2009;Miteva, et al, 2009;Tamandani, et al, 2009;Wei, et al, 2009;Zhao, et al, 2009;Wu, et al, 2009;Ben, et al, 2011;Liu, et al, 2011;Welsh, et al, 2011;Yang, et al, 2011;do CarmoVasconcelosde Carvalho V, et al, 2012;Huang, et al, 2012;Kaarvatn, et al, 2012;Roszak, et al, 2012;Sima, et al, 2012;Tao, et al, 2012;Jaiswal, et al, 2013;Sun, et al, 2013;Wang, et al,2013;Saxena, et al,2014;Jafarzadeh, et al,2015;Sun, et al,2015;Winchester, et al,2015;Yin, et al,2015)(see Fig. 1).…”

Kronik Hepatit B ve C Enfeksiyonu ile Interlokin-2 (-330) Gen Polimorfizmi Arasindaki Iliskinin Arastirilmasi

“…(27) Graves hastalığı olan kişilerde IL-2 GG genotip sıklığını kontrol grubuna göre anlamlı düzeyde daha yüksek bulmuşlar ve bu hastalarda IL-2 gen ifadesinin arttığını bildirmişlerdir. İran'da yapılan bir başka çalışmada da multiple sklerozlu hastalarda IL-2 -330 T alleline sahip kişilerin hastalığa karşı daha duyarlı olduğu belirlenmiştir (28 (34). Ülkemizde ise hepatit B ve C hastalığı ile IL-2 -330 polimorfizmi arasındaki ilişkiyi araştıran herhangi bir çalışmaya rastlanılmamıştır.…”