Polymorphism at rs9264942 is associated with HLA-C expression and inflammatory bowel disease in the Japanese
Polymorphism at rs9264942 is associated with HLA-C expression and inflammatory bowel disease in the Japanese
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DOI：
10.1038/s41598-020-69370-8
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发表时间：
2020-07-24
影响因子：
4.6
通讯作者：
Ota，Masao
中科院分区：
文献类型：
--
作者：
Suzuki，Hiroshi;Joshita，Satoru;Ota，Masao
rs 9264942处的表达数量性状位点（eQTL）单核苷酸多态性（SNP）与欧洲人的人类白细胞抗原（HLA）-C表达早期相关。HLA-C也与日本人的炎症性肠道疾病（IBD）风险有关。本研究检测了rs 9264942处的eQTL SNP是否可以调节HLA-C表达，以及HLA-C*12：02~B*52：01~ DRB 1 *15：02等位基因中携带的IBD风险的rs 9264942处的eQTL SNP和rs 2270191、rs3132550和rs6915986处的3个SNP单倍型是否与日本人IBD相关。rs 9264942的CC或CT基因型的CD 3e + CD 8a+淋巴细胞上的HLA-C表达显著高于TT基因型。四个SNPs的TACC单倍型与溃疡性结肠炎（UC）的强烈易感性相关，但与克罗恩病（CD）的保护作用以及疾病的临床结果相关。CGTT单倍型UC保护作用显著，CD易感性不显著; CGCT单倍型UC保护作用显著消失，CD易感性显著。总之，我们的研究结果支持rs 9264942处的eQTL SNP调节日本人HLA-C的表达，并表明处于强连锁不平衡的4个SNP可能是与IBD易感性和疾病结果相关的特定HLA单倍型HLA-C*12：02~B*52：01~ DRB 1 *15：02的替代标记候选者。
An expression quantitative trait locus (eQTL) single-nucleotide polymorphism (SNP) at rs9264942 was earlier associated with human leukocyte antigen (HLA)-C expression in Europeans. HLA-C has also been related to inflammatory bowel disease (IBD) risk in the Japanese. This study examined whether an eQTL SNP at rs9264942 could regulate HLA-C expression and whether four SNP haplotypes, including the eQTL SNP at rs9264942 and three SNPs at rs2270191, rs3132550, and rs6915986 of IBD risk carried in the HLA-C*12:02~B*52:01~DRB1*15:02 allele, were associated with IBD in the Japanese. HLA-C expression on CD3e+CD8a+lymphocytes was significantly higher for the CC or CT genotype than for the TT genotype of rs9264942. The TACC haplotype of the four SNPs was associated with a strong susceptibility to ulcerative colitis (UC) but protection against Crohn’s disease (CD) as well as with disease clinical outcome. While UC protectivity was significant but CD susceptibility was not for the CGTT haplotype, the significance of UC protectivity disappeared but CD susceptibility reached significance for the CGCT haplotype. In conclusion, our findings support that the eQTL SNP at rs9264942 regulates HLA-C expression in the Japanese and suggest that the four SNPs, which are in strong linkage disequilibrium, may be surrogate marker candidates of a particular HLA haplotype, HLA-C*12:02~B*52:01~DRB1*15:02, related to IBD susceptibility and disease outcome.