Evaluation of human leukocyte antigen-A (HLA-A), other non-HLA markers on chromosome 6p21 and risk of nasopharyngeal carcinoma.
Evaluation of human leukocyte antigen-A (HLA-A), other non-HLA markers on chromosome 6p21 and risk of nasopharyngeal carcinoma.
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DOI：
10.1371/journal.pone.0042767
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hildesheim A
中科院分区：
文献类型：
--
作者：
Hsu WL;Tse KP;Liang S;Chien YC;Su WH;Yu KJ;Cheng YJ;Tsang NM;Hsu MM;Chang KP;Chen IH;Chen TI;Yang CS;Goldstein AM;Chen CJ;Chang YS;Hildesheim A
人类白细胞抗原（HLA）基因（位于染色体6p 21的主要组织相容性复合体[MHC]区域）与NPC之间的关联已经知道一段时间了。最近，在台湾和中国进行的两项全基因组关联研究（GWAS）证实，NPC关联的最强有力证据被定位到MHC区域。然而，目前尚不清楚这些发现是否反映了与人类白细胞抗原（HLA）基因和/或该基因丰富区域中的其他基因的直接关联。为了更好地了解6号染色体MHC区域内NPC的遗传相关性，我们进行了一项评估，合并了两项先前在台湾进行的NPC病例对照研究（N = 591例和N = 521例对照）。 对台湾NPC GWAS中6p 21内鉴定的12个显著SNPs和HLA-A基因（外显子2和3）进行基于PCR的基因分型。在确认两项研究之间的同质性后，通过logistic回归估计合并优势比（OR）和95%置信区间（CI）。我们发现，HLA-A（p趋势= 0.0006）和rs 29232（在GABBR 1基因内; p趋势= 0.005）是NPC的独立危险因素，调整后的年龄，性别，研究和对方。 NPC风险在HLA-A*0207风险等位基因纯合子和rs 29232风险等位基因（A）携带者中最高。我们的研究表明，GWAS中与NPC显著相关的大多数SNPs反映了先前确定的HLA-A相关性。然而，rs 29232（GABBR 1）的独立效应仍然存在，这表明该区域内的其他基因可能与NPC风险相关。
The association between human leukocyte antigen (HLA) genes (located in the Major Histocompatibility Complex [MHC] region of chromosome 6p21) and NPC has been known for some time. Recently, two genome-wide association studies (GWAS) conducted in Taiwan and China confirmed that the strongest evidence for NPC association was mapped to the MHC region. It is still unclear, however, whether these findings reflect direct associations with Human Leukocyte Antigen (HLA) genes and/or to other genes in this gene-rich region. To better understand genetic associations for NPC within the MHC region of chromosome 6, we conducted an evaluation that pooled two previously conducted NPC case-control studies in Taiwan (N = 591 cases and N = 521 controls). PCR-based genotyping was performed for 12 significant SNPs identified within 6p21 in the Taiwan NPC GWAS and for the HLA-A gene (exons 2 and 3). After confirming homogeneity between the two studies, pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. We found that HLA-A (p-trend = 0.0006) and rs29232 (within the GABBR1 gene; p-trend = 0.005) were independent risk factors for NPC after adjustment for age, gender, study and each other. NPC risk was highest among individuals who were homozygous for the HLA-A*0207 risk allele and carriers of the rs29232 risk allele (A). Our study suggests that most of the SNPs significantly associated with NPC from GWAS reflect previously identified HLA-A associations. An independent effect of rs29232 (GABBR1), however, remained, suggesting that additional genes within this region might be associated with NPC risk.