The 14bp‐deletion allele in the HLA‐G gene confers susceptibility to the development of hepatocellular carcinoma in the Brazilian population

Abstract

Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule involved in tumor escape mechanisms. Considering that the HLA-G 14bp insertion/deletion polymorphism is located at the 3' untranslated region (3'UTR) in exon 8, and since it has been associated with the magnitude of HLA-G production, we studied the association of 14bp insertion/deletion polymorphism with the risk of developing hepatocellular carcinoma (HCC). A total of 109 HCC patients followed at the University Hospital, Faculty of Medicine of Ribeirão Preto, São Paulo, Brazil, and 202 healthy controls from the same geographic area were genotyped for the 14bp insertion/deletion polymorphism using polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis. Compared to controls, the frequency of the 14bp deletion allele was overrepresented in HCC patients (65% versus 56%, respectively, P = 0.0326). The 14bp deletion conferred an odds ratio (OR) of 1.46 [95% confidence interval (CI): 1.04-2.05]. Similarly, the deletion/deletion genotype was marginally overrepresented in HCC patients (45% versus 35% in controls, P = 0.0871), conferring an OR of 1.54 (95% CI: 0.96-2.48). The frequencies of the deletion/insertion or insertion/insertion genotypes observed in patients were not statistically different from those observed in controls (P > 0.05). Our results suggest that the 14bp-deletion allele in HLA-G gene is associated with HCC susceptibility in a Brazilian population.

HLA-G genetic variants and hepatocellular carcinoma: a meta-analysis

“…In contrast, all the remaining nonAsian samples had MAF > 0.30, with a mean frequency of 0.40 (whereas the Asian samples had a mean of 0.24) and a range between 0.33 in CLM and YRI to 0.49 in the Tunisian sample (Laaribi et al, 2015) (Table 2). Therefore, the F ST indexes revealed a small but significant (0.05 > F ST > 0.09) presence of genetic diversity when comparing the Korean (Kim et al, 2013) sample to some of the other non-Asian admixed samples, namely the reference MXL sample and Brazilian samples (Cordero et al, 2009;Teixeira et al, 2013;da Silva et al, 2014). In contrast, all non-Asian samples and the Chinese sample (Jiang et al, 2011) had very low pairwise F ST indexes (F ST < 0.05) when compared ( Table 2).…”

The Role of HLA-G Molecule and HLA-G Gene Polymorphisms in Tumors, Viral Hepatitis, and Parasitic Diseases

“…The 14-bpDEL allele was associated with susceptibility to hepatocellular carcinoma in Brazilian ( 83 ) and Chinese ( 84 ) patients, but not in Korean patients ( 84 ). In addition, Chinese patients exhibiting the 14-bpDEL/DEL genotype presented increased HLA-G expression in hepatocellular carcinoma specimens ( 84 ).…”

Genetic association between HLA-G 14-bp polymorphism and diseases: A systematic review and meta-analysis

“…Articles included comprised case-control studies involving the HLA-G 3′UTR 14-bp polymorphism and clinical situations/ diseases. Studies were grouped according to clinical characteristics, pathogenesis and immune response as follow: (1) cancer 2 -B-Cell Lymphoma [27], Breast Cancer [28][29][30][31][32], Cervical Cancer [33][34][35][36], Colorectal cancer [37], Esophageal Cancer [38], Hepatocellular Carcinoma [39][40][41], Head and Neck Squamous-Cell Carcinoma (HNSCC) [42], Lung Cancer [43], Neuroblastoma [44], Papillary Thyroid Cancer [45] and Prostate Cancer [46]; (2) autoimmune diseases 3 -Hashimoto's Thyroiditis [45], Juvenile Idiopathic Arthritis [47], Multiple Sclerosis [48][49][50][51], Non-segmental Vitiligo [52], Pemphigus Vulgaris [53], Rheumatoid Arthritis [47,[54][55][56][57][58], Systemic Lupus Erythematosus (LES) [59][60][61][62][63][64][65][66][67] and Type 1 Diabetes [68]…”