Tian W, Zhu F-M, Wang W-Y, Cai J-H, Zhang W, Li L-X, Liu K-L, Jin H-K, Wang F
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.
Tissue Antigens. 2015 Jul;86(1):15-20. doi: 10.1111/tan.12576. Epub 2015 May 4.
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-A02:07, HLA-A11:01 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.
在本研究中，我们对来自中国南方湖南省的930例鼻咽癌（NPC）患者和1134名正常对照进行了人类白细胞抗原A（HLA-A）基因座第2至4外显子的测序。结果发现HLA-A02:07、HLA-A11:01与鼻咽癌之间存在非常显著的关联[分别为25.7%对16.18%；优势比，OR（95%置信区间，CI）=1.79（1.54 - 2.09），P<0.0001以及21.1%对30.42%，OR（95%CI）=0.61（0.53 - 0.70），P<0.0001]。对这些关联背后分子基础的进一步分析表明，HLA-A蛋白α2螺旋第99位密码子处的半胱氨酸（C）可能有害，并赋予患鼻咽癌的风险。在中国南方人群中发现了令人信服的证据，表明一种罕见等位基因HLA-A*31:01与鼻咽癌呈负相关[0.22%对2.12%，OR（95%CI）=0.1（0.04 - 0.28），P<0.0001]。编码HLA-A蛋白α1螺旋第56位密码子精氨酸（R）的rs1059449 - A被认为对于这种与鼻咽癌的负相关模式至关重要。对一部分鼻咽癌病例（N = 632）和正常对照（N = 712）检测了抗病毒衣壳抗原（anti-VCA）免疫球蛋白A（IgA），两组之间anti-VCA IgA血清阳性率存在非常显著差异[67.56%对6.46%，OR（95%CI）=30.16（21.42 - 42.46），P<0.0001]。然而，两组中anti-VCA IgA血清阳性率与HLA-A等位基因分型均无相关性。
