New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia

Previous studies have revealed the association between SNPs located on human leukocyte antigen (HLA) class II genes, including HLA-DP and HLA-DQ, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. HLA-DP alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between HLA-DP and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) HLA-DPA1 and HLA-DPB1 genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele HLA-DPB1*09 ratio 01 (P = 1.36 x 10(-6); OR= 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB1*02 ratio 01 (P = 5.22 x 10(-6); OR = 0.68; 95% CI, 0.58-0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, DPB1*02 ratio 01 was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55 x 10(-7); OR = 0.50; 95% CI, 0.39-0.65). Trans-ethnic association analyses identified Asian-specific associations of HLA-DP alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma.published_or_final_versio

High prevalence of circulating DS-1-like human rotavirus A and genotype diversity in children with acute gastroenteritis in Thailand from 2016 to 2019

Background: Human rotavirus A (RVA) infection is the primary cause of acute gastroenteritis (AGE) in infants and young children worldwide, especially in children under 5 years of age and is a major public health problem causing severe diarrhea in children in Thailand. This study aimed to investigate the prevalence, genotype diversity, and molecular characterization of rotavirus infection circulating in children under 15 years of age diagnosed with AGE in Thailand from January 2016 to December 2019. Methods: A total of 2,001 stool samples were collected from children with gastroenteritis (neonates to children <15 years of age) and tested for RVA by real-time polymerase chain reaction (RT-PCR). Amplified products were sequenced and submitted to an online genotyping tool for analysis. Results: Overall, 301 (15.0) stool samples were positive for RVA. RVA occurred most frequently among children aged 0-24 months. The seasonal incidence of rotavirus infection occurred typically in Thailand during the winter months (December-March). The G3P8 genotype was identified as the most prevalent genotype (33.2%, 100/301), followed by G8P8 (10.6%, 32/301), G9P8 (6.3%, 19/301), G2P4 (6.0%, 18/301), and G1P6 (5.3%, 16/301). Uncommon G and P combinations such as G9P4, G2P8, G3P4 and G3P9 were also detected at low frequencies. In terms of genetic backbone, the unusual DS-1-like G3P8 was the most frequently detected (28.2%, 85/301), and the phylogenetic analysis demonstrated high nucleotide identity with unusual DS-1-like G3P8 detected in Thailand and several countries. Conclusions: A genetic association between RVA isolates from Thailand and other countries ought to be investigated given the local and global dissemination of rotavirus as it is crucial for controlling viral gastroenteritis, and implications for the national vaccination programs. © 2021 Pasittungkul et al