Sequence-based typing of HLA-A gene in 930 patients with nasopharyngeal carcinoma in Hunan province, southern China.
In this study, we typed 930 cases of nasopharyngeal carcinoma (NPC) and 1134 normal controls recruited from Hunan province, southern China for human leukocyte antigen-A (HLA-A) locus by sequencing exons 2-4. Very significant associations between HLA-A*02:07, HLA-A*11:01 and NPC were established [25.7% vs 16.18%; odds ratio, OR (95% confidence interval, CI) = 1.79 (1.54-2.09), P < 0.0001 and 21.1% vs 30.42%, OR (95% CI) = 0.61 (0.53-0.70), P<0.0001, respectively]. Further analysis of the molecular basis underlying these associations suggests that cysteine (C) at codon 99 of α2-helix of HLA-A protein is probably deleterious and confers risk to NPC. Convincing evidence was uncovered for negative association of a rare allele in southern Chinese populations, HLA-A*31:01, with NPC [0.22% vs 2.12%, OR (95% CI) = 0.1 (0.04-0.28), P < 0.0001]. rs1059449-A, which encodes arginine (R) at codon 56 of α1-helix of HLA-A protein, was postulated to be crucial for such a pattern of negative association with NPC. A subset of NPC cases (N = 632) and normal controls (N=712) were tested for anti-virus capsid antigen (anti-VCA) immunoglobulin A (IgA), very significant difference in seropositivity for anti-VCA IgA was observed between the two groups [67.56% vs 6.46%, OR (95% CI) = 30.16 (21.42-42.46), P < 0.0001]. However, seropositivity for anti-VCA IgA did not correlate with HLA-A allelic typing in both groups.
Immunogenetics Research Group, Department of Immunology, College of Basic Medical Sciences, Central South University, Changsha, China.|Laboratory of Cellular and Molecular Biology, College of Basic Medical Sciences, Central South University, Changsha, China.
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W
Tian
HLA Typing Laboratory, Blood Center of Zhejiang Province, Hangzhou, China.|Key Laboratory of Blood Safety Research, Ministry of Health, Hangzhou, China.
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FM
Zhu
Immunogenetics Research Group, Department of Immunology, College of Basic Medical Sciences, Central South University, Changsha, China.
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WY
Wang
Immunogenetics Research Group, Department of Immunology, College of Basic Medical Sciences, Central South University, Changsha, China.
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JH
Cai
HLA Typing Laboratory, Blood Center of Zhejiang Province, Hangzhou, China.|Key Laboratory of Blood Safety Research, Ministry of Health, Hangzhou, China.
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W
Zhang
Immunogenetics Research Group, Department of Immunology, College of Basic Medical Sciences, Central South University, Changsha, China.|Laboratory of Cellular and Molecular Biology, College of Basic Medical Sciences, Central South University, Changsha, China.
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LX
Li
Department of Nuclear Medicine, Hunan Cancer Hospital, The Affiliated Cancer Hospital of XiangYa School of Medicine of Central South University, Changsha, China.
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Liu
Department of Radiotherapy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of XiangYa School of Medicine of Central South University, Changsha, China.
H-K
HK
Jin
Immunogenetics Research Group, Department of Immunology, College of Basic Medical Sciences, Central South University, Changsha, China.
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F
Wang
D000328:Adult; D000483:Alleles; D000914:Antibodies, Viral / Q000097:blood*; D000956:Antigens, Viral / Q000097:blood; D036022:Capsid Proteins / Q000097:blood; D002277:Carcinoma; D016022:Case-Control Studies; D002681:China; D003062:Codon; D005091:Exons; D005260:Female; D005787:Gene Frequency; D015234:HLA-A Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D017433:Protein Structure, Secondary; D012306:Risk; D017422:Sequence Analysis, DNA
D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D003062:Codon; C041788:Epstein-Barr viral capsid antigen; D015234:HLA-A Antigens; D007070:Immunoglobulin A
association; human leukocyte antigen-A; nasopharyngeal carcinoma; sequence-based typing; southern Chinese population