Association of CTLA‐4, TNF alpha and IL 10 polymorphisms with susceptibility to hepatocellular carcinoma

Abstract

Our aim was to evaluate the association of genetic polymorphisms of immunoregulatory molecules with susceptibility to hepatocellular carcinoma (HCC). The polymorphisms in CTLA‐4 (−318 T/C, CT60 G/A), TNF (−238 G/A, −308 G/A) and IL10 (−592 C/A, −819 C/T) were genotyped by PCR and DNA sequencing. The functional relevance of the polymorphisms was examined by ELISAs, in vitro lymphocyte proliferation assay and cytotoxic assay. The CTLA‐4 −318 TC/TT, CTLA‐4 CT60 GG, IL10 −592 CA and −819 CT/TT variants, CTLA‐4 −318 T and IL 10 −819 T alleles were positively associated with HCC risk (P < .05). While TNF −238 AA variant, TNF −238 A allele were associated with decreased risk of HCC (P < .05). Furthermore, combinations of CTLA‐4 −318 TC/TT and TNF −238 GG/GA; CTLA‐4 −318 TC/TT and IL 10 −819 CC; CTLA‐4 −318 CC and IL 10 −819 CT/TT in patients with HCC were statistically significant (P < .05). Peripheral blood mononuclear cells (PBMCs) carrying −318 TC/TT genotypes exhibited significantly lower proliferation rates, decreased IL‐2, IL‐4 levels, fewer cytolytic activities and elevated TGF‐β levels. For IL 10 −819 C/T, the CC genotype was significantly associated with higher proliferation rate, decreased TGF‐β, IL‐10 levels and higher cytolytic activities (P < .05). For TNF −238 G/A, the AA genotype only had association with serum IL‐2, IL‐4 (P < .05). In addition, we also found that CTLA‐4 −318 T/C, IL‐10 −819 T/C variants, combinations of CTLA‐4 −318 CC with IL 10 −819 CT or TT, CTLA‐4 −318 TC or TT with IL 10 −819 CT or TT were associated with the severity of HCC. These findings suggest that CTLA‐4 −318 TC/TT and IL 10 −819 CT/TT could promote the pathogenesis of HCC, which might be related with down‐regulation of Th1/Th2‐type cytokines and/or up‐regulation of Th3‐type cytokines.

Direct Relationship between Interleukin-10 Gene Polymorphism and Hepatocellular Carcinoma Complicated by Direct Acting Antiviral Treatment of Hepatitis C Virus

“…These results are in agreement with those of a previous study (Wang et al, 2019) who found that CT was the most common genotype in HCC group (P value < 0.05). Few studies (Aroucha et al, 2016;Wang et al, 2019) found that T allele was the most common allele in HCC.…”

“…These results are in agreement with those of a previous study (Wang et al, 2019) who found that CT was the most common genotype in HCC group (P value < 0.05). Few studies (Aroucha et al, 2016;Wang et al, 2019) found that T allele was the most common allele in HCC. Moreover, reports (Li et al, 2018;Maurya et demonstrated that TT genotype of IL-10(−819) gene was found in 20 patients (50%) with HCV infection and 25 patients (62.5%) with HCC.…”

MFAP2 Promotes the Proliferation of Cancer Cells and Is Associated With a Poor Prognosis in Hepatocellular Carcinoma

“…Recently, some studies have focused on the relationship between CTLA4 SNPs and susceptibility to HCC, and Wang's research demonstrated that CTLA4 could affect susceptibility to HCC via changing the immune status of the individuals. 34 TISIDB results indicated that MFAP2 expression is closely related to Tregs and some immunological checkpoints which have recently received more and more attention, such as CTLA4, TIGIT in HCC. Therefore, inhibitors that target these immune checkpoints might be particularly effective in the treatment of HCC patients, especially when used in combination with MFAP2 inhibitors.…”

Genetic polymorphisms and protein levels in vocal fold leukoplakia: a systematic review

“…Concerning the -1082 A/G IL-10 SNP, there was a lack of association between this genetic polymorphism and VFL. These three IL-10 SNPs are located in the promoter region of the gene ( 27 ). The T allele of the -819 T/C SNP, the A allele of the -592 A/C IL-10 SNP, and the A allele of the -1082 A/G IL-10 SNP were associated with lower IL-10 concentration, while the CCG haplotypes of these SNPs, respectively, were related to higher IL-10 secretion ( 28 ).…”