Novel missense mutation c.797T>C (p.Met266Thr) gives rise to the rare B(A) phenotype in a Chinese family.

BACKGROUND AND OBJECTIVES: B(A) phenotype is usually formed by nucleotide mutations in the ABO*B.01 allele, with their products exhibiting glycosyltransferases (GTs) A and B overlapping functionality. We herein report a B(A) allele found in a Chinese family. MATERIALS AND METHODS: The entire ABO genes of the probands, including flanking regulatory regions, were sequenced through PacBio third-generation long-read single-molecule real-time sequencing. 3D molecular models of the wild-type and mutant GTB were generated using the DynaMut web server. The effect of the mutation on the enzyme function was predicted by PROVEAN and PolyPhen2. The predictions of stability changes were performed using DynaMut and SNPeffect. RESULTS: Based on serological and sequencing features, we concluded the two probands as possible cases of the B(A) phenotype. Crystallization analysis showed that Thr266 substitution does not disrupt the hydrogen bonds. However, some changes in interatomic contacts, such as loss of ionic interactions and hydrophobic contacts, and addition of weak hydrogen bonds, may have affected protein stability to some extent. This mutation was predicted to have a benign effect on enzyme function and slightly reduce protein stability. CONCLUSION: The probands had the same novel B(A) allele with a c.797T>C (p.Met266Thr) mutation on the ABO*B.01 backbone.

Association between the Genetic Polymorphisms of CCL2, CCL5, CCL8, CCR2, and CCR5 with Chronic Hepatitis C Virus Infection in the Chinese Han Population.

Hepatitis C virus (HCV) infection is a global public health burden. Chronic HCV infection leads to the development of fibrosis, cirrhosis, liver cancer, and liver failure over time. A total of 250 patients with chronic HCV infection and 299 healthy blood donors were recruited. Sixteen candidate single nucleotide polymorphisms (SNPs) in chemokine (C-C motif) ligand 2 (CCL2), CCL5, CCL8, C-C chemokine receptor 2 (CCR2), and CCR5 were genotyped in all participants. The rs1024610 AA genotype was significantly associated with decreased susceptibility to chronic HCV infection. Aspartate aminotransferase (AST) levels, AST/platelet ratio index, and the fibrosis 4 score were significantly lower in the CCL2 rs1024610 T allele and haplotype ATGC carriers. Moreover, expression levels of collagen IV (C-IV) and laminin (LN) were significantly higher in patients with the CCL5 rs2280788 C allele compared to the non-carriers. Similarly, the expression levels of C-IV, LN, and hyaluronic acid were significantly higher in patients with the CCL5 haplotype, TGCT. No significant differences were identified between the SNPs/haplotypes and plasma levels of CCL2, CCL5, CCL8, CCR2, and CCR5 in the healthy controls, and the rs1024610 allele alteration had no effect on CCL2 promoter activity. This is the first study to report an association between CCL2 rs1024610 and the risk of chronic HCV infection in the Chinese Han population. rs1024610 and ATGC haplotype in CCL2 were reasonable candidate markers of liver abnormalities. rs2280788 and TGCT haplotype in CCL5 are likely to play a significant role in liver fibrosis during chronic HCV infection.

Associations between human leukocyte antigen C locus polymorphism and psoriatic arthritis in populations of European and Middle Eastern descent: a meta-analysis.

BACKGROUND: Gene-disease association between human leukocyte antigen (HLA)-C locus polymorphism and psoriatic arthritis (PsA) remains controversial. OBJECTIVE: Evaluate the relationship between HLA-C locus polymorphism and PsA in populations of European and Middle Eastern descent. SEARCH METHODS: PubMed, PMC, Elsevier and Google Scholar databases from 1980 to January 2020. The search was limited to articles in English. SELECTION CRITERIA: Case-control studies (with unrelated participants) that had allele/genotype data on the association between HLA-C locus polymorphism and PsA susceptibility. DATA COLLECTION AND ANALYSIS: Two investigators searched independently in searching the literature. Disagreements were resolved by discussion and consultation with a third researcher. The Q-Genie tool was used to assess the quality of articles. RESULTS: Twenty-five studies met the inclusion criteria. At the allelic level, three alleles were associated with an increased risk of PsA and five were associated with a reduced risk. At the phenotypic level, four alleles were associated with increased risk of PsA and three were associated with a reduced risk. At both the allelic and phenotypic levels, the results revealed that HLA-C*04 played a protective role in PsA (The pooled odds ratio [OR] is 0.66 for allelic level and 0.63 for phenotypic level), while HLA-C*02, *06 and *12 increased the risk of suffering from PsA (The pooled ORs of C*02, *06 and *12 are 2.21, 2.63 and 1.49 for allelic level, and 1.79, 2.96 and 2.25 for phenotypic level, respectively). CONCLUSION: The pooled results showed a significant association between PsA and the HLA-C gene in populations of European and Middle Eastern descent. At both the allelic and phenotypic levels, the HLA-C*02, *06 and *12 may contribute to susceptibility to PsA, while HLA-C*04 may confer a protective role against PsA. REGISTRATION: Not registered. CONFLICT OF INTEREST: None.