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.

Polymorphisms in the promoter regions of RHD and RHCE genes in the Chinese Han population.

BACKGROUND AND OBJECTIVES: The Rh blood group system is the most polymorphic human blood group system. Previous studies have investigated variants in the RHD and RHCE promoter. The relevance of these variants to the Chinese Han population is further clarified in this study. MATERIALS AND METHODS: In total, 317 donors (223 Rh D-positive [D+], including 20 Del and 94 Rh D-negative [D-]) were randomly selected. The promoter regions and exon 1 of RHD and RHCE were amplified through polymerase chain reaction (PCR) whose products were directly sequenced using forward and reverse primers. RESULTS: Expected PCR products of the RHD promoter and exon 1 were amplified in 223 D+ individuals, including 20 Del individuals, and were absent in 81 of 94 D- individuals. Expected PCR products of RHCE were observed in all donors. Two single nucleotide variants (SNVs) were observed in the RHD promoter region. Moreover, 11 SNVs were observed in the promoter and exon 1 of RHCE. rs4649082, rs2375313, rs2281179, rs2072933, rs2072932, rs2072931 and rs586178 with strong linkage disequilibria were significantly different between the D+ and D- groups. [A;C] was the most common haplotype in the RHD promoter (NC_000001.11:g.[-1033A>G;-831C>T]). [G;T;T;A;T;A;C;G;A;C;G] was the most predominant haplotype in both total and D- groups. In D+ individuals, [A;C;T;G;C;G;C;G;C;C;C] was the most frequent haplotype in the RHCE promoter (NC_000001.11:g.[-1080A>G;-958C>T;-390T>C;-378G>A;-369C>T;-296G>A;-144C>G;-132G>A;-122C>A;28C>T;48C>G]). CONCLUSION: We speculate that the SNVs/haplotypes found in this article cannot significantly affect gene expression. The present study findings should help elucidate the molecular basis of the polymorphic expression of RHD and RHCE promoter regions.

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.

Platelet indices significantly correlate with liver fibrosis in HCV-infected patients.

AIM: A total of 241 patients with chronic HCV infection were recruited to investigate the association between liver fibrosis and PLT counts, as well as with MPV, PDW and P-LCR indices. METHODS: The determination of PLT indices was carried out using a Sysmex XT-1800i automated hematology analyzer. Serological tests for HA, LN, C-IV and PIIINP were performed in 210 patients. The liver stiffness was measured in 69 patients by transient elastography (FibroScan). RESULTS: The analysis showed that the four serum fibrosis markers were negatively correlated with PLT counts, but positively correlated with the MPV, PDW and P-LCR values. Moreover, a similar pattern was found after analyzing the FibroScan measurements, which were negatively correlated with PLT counts, but positively correlated with MPV, PDW and P-LCR values. We subdivided the HCV-infected patients into mild and advanced fibrosis groups. The PLT counts were significantly decreased and the MPV, PDW and P-LCR values were significantly increased in the advanced fibrosis group when compared with the mild fibrosis group. CONCLUSIONS: Our results demonstrate that not only the PLT counts but also the MPV, PDW and P-LCR indices significantly correlate with liver fibrosis in HCV-infected patients. Therefore, these indices may be useful laboratory measures for evaluating liver fibrosis progression.

Association between the polymorphism of HLA and ESRD in Dalian Han population located in north of China.

BACKGROUND: End-stage renal disease (ESRD), the last stage of chronic renal failure, is a global health problem. The number of ESRD patients worldwide is increasing faster than the number of kidneys available per year for renal transplantation. Most of the ESRD patients are awaiting renal transplantation. The immune response to the transplanted kidney is directed mainly against mismatched human leukocyte antigen (HLA) glycoproteins expressed on donor tissues. Thus, the analysis of HLA allele and haplotype polymorphisms is valuable not only for identifying ESRD susceptibility factors but also to improve graft survival. METHODS: In this study, 163 Han ESRD patients were recruited to participate. The blood samples were genotyped by sequence-specific oligonucleotide method. A group of 14,529 healthy Chinese Han individuals registered at the Dalian Blood Center as bone marrow donors, living in the same region and of the same ethnicity, were used as controls. RESULTS: We found that only one allele, HLA-DRB1*12, showed a positive association with ESRD (p = 0.004, pc = 0.028, odds ratio = 1.530, 95% confidence interval = 1.147-2.041); A*02-B*40-DRB1*09, A*02-B*40-DRB1*12, A*24-B*15-DRB1*12, and B*40-DRB1*12 were significantly more frequent in ESRD patients after Bonferroni correction (pc < 0.05). CONCLUSION: They were potentially valuable predictors for evaluating the risk of ESRD in the Dalian Han population.

Atypical Chemokine Receptor 1 polymorphism cannot be used as an indicator of liver fibrosis progression in Hepatitis C virus positive patients.

BACKGROUND & OBJECTIVE: Atypical chemokine receptor 1(ACKR1) represents an atypical chemokine receptor that can bind promiscuously to various chemokines. Chemokines play a crucial role to recruit leukocyte subsets migration through the endothelium and into liver against the virus during the progression of hepatitis C virus (HCV) infection. Most HCV positive patients can lead to liver fibrosis. Hyaluronic acid (HA), laminin (LN), collagen IV(C-IV) and amino-terminal pro-peptide of Type-III pro-collagen (PIII NP) are indices of the extent of liver fibrosis. The aim of this study was to investigate the association between ACKR1 polymorphism and liver fibrosis with these four serum liver markers in HCV positive patients. METHODS: From April 2015 to December 2015, a total of 210 patients (109 males and 101 females) with chronic HCV infection at Dalian Infectious Hospital were recruited to participate in this study. ACKR1 genotyping was using TaqMan probes method. HA, LN, C-IV and PIII NP were detected by using diagnostic kits. RESULTS: We compared serum levels of HA, LN, C-IV and PIII NP between FY*A/FY*A and FY*A/FY*B patients and the differences were not significant (P=0.905, P=0.298, P=0.880 and P=0.470, respectively). CONCLUSIONS: This study has attempted to elucidate the role of ACKR1 polymorphism in liver fibrosis progression of HCV infection, our results demonstrated that ACKR1 polymorphism is not directly associated with the fibrogenesis in HCV positive patients.

Atypical Chemokine Receptor 1 Polymorphism can not Affect Susceptibility to Hepatitis C Virus.

BACKGROUND: Hepatitis C virus has infected 130 to 150 million individuals globally. Atypical chemokine receptor 1 has become a focus of research because of its diverse roles in different diseases. However, little is known regarding the association of atypical chemokine receptor 1 polymorphism with susceptibility to hepatitis C virus. AIMS: To determine the association of an atypical chemokine receptor 1 polymorphism (rs12075) with hepatitis C virus susceptibility. STUDY DESIGN: Case-control study. METHODS: We collected blood samples from 231 patients infected with hepatitis C virus and 239 blood donors as control subjects. Genotyping of atypical chemokine receptor 1 was performed using a 5'-nuclease assay with TaqMan-minor groove binding probes. Comparisons between hepatitis C virus-infected patients and control subjects were assessed using Fisher's exact test. RESULTS: The genotype frequencies of FY*A/FY*A, FY*A/FY*B and FY*B/FY*B were 86.1%, 13.9% and 0% in the patient group, and 86.2%, 13.4% and 0.4% in the control group, respectively. The difference in atypical chemokine receptor 1 genotype frequencies between hepatitis C virus-infected patients and control group was not significant (p=1.00, OR=1.004, 95% CI=0.594-1.695). FY*A and FY*B allele frequencies were 93.1% and 6.9% in the patient group, and 92.9% and 7.1% in the control group, respectively. The difference in atypical chemokine receptor 1 allele frequencies between hepatitis C virus-infected patients and the control group was not significant (p=1.00, OR=0.972, 95% CI=0.589-1.603). CONCLUSION: Our result indicates that atypical chemokine receptor 1 polymorphism (rs12075) does not affect susceptibility to hepatitis C virus.