No association of HLA-DRB1 and TNF alleles in Mexican patients with autoimmune hepatitis

• Published in: Genes and immunity Vol. 20; no. 8; pp. 678 - 683
• Main Authors: Mendoza-Carrera, Francisco, Gastélum-Meza, Miguel Ángel, Ramírez-García, Jesús, Dávalos-Cobián, Carlos, Castro-Martínez, Xochitl Helga, Arellano-Olivera, María Inmaculada Concepción, Hernández-Ramos, Luis Eduardo, Leal-Cortés, Caridad
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.11.2019
• Subjects: Alleles; Allelomorphism; Analysis; Associations; Blood donors; Chronic active hepatitis; Drb1 protein; Environmental factors; Female; Genetic aspects; Haplotypes; Health aspects; Hepatitis; Hepatitis, Autoimmune - genetics; Histocompatibility antigen HLA; Histocompatibility antigens; HLA histocompatibility antigens; HLA-DRB1 Chains - genetics; Humans; Male; Medical research; Medicine, Experimental; Mexico; Odds Ratio; Population genetics; Population studies; Tissue typing; Tumor necrosis factor; Tumor Necrosis Factor-alpha - genetics; Mexico
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/s41435-019-0086-8

HLA-DRB1 alleles has been found implicated in susceptibility to autoimmune hepatitis (AIH) in populations from different genetic backgrounds. In Mexicans, HLA-DRB1*04:04 is recognized as a risk allele for AIH but, to date, there is no high-resolution data supporting this association. Also, the association of other nonclassical HLA genes, such as TNF-LTA locus, have not, to our knowledge, been evaluated in this population. The association of HLA-DRB1 alleles determined by sequence-based typing and two polymorphisms in the TNF locus with AIH in a sample of Mexican patients was evaluated. Fifty-six patients from Guadalajara, Mexico, diagnosed with AIH and 115 age-gender matched healthy volunteer blood donors, were genotyped for HLA-DRB1 by the sequencing exon 2 and for TNFA-308G>A and LTA + 252A>G polymorphisms. Increased frequencies of both HLA-DRB1*04:04:01 and *16:02:01:01 alleles (OR = 2.91; 95% CI = 1.08-7.84) and the haplotype (DRB1-TNFA-LTA) *04:04:01-G-A (OR = 5.33; 95% CI = 1.32-21.49) were observed in AIH patients. However, after corrections for multiple comparisons, associations were not significant. In conclusion, our study does not support the association of HLA-DRB1*04:04:01 with the susceptibility to AIH in Mexican population. More studies including patients from other Mexican regions and considering other genetic, immunological, and environmental factors should be performed.