Genetic variants in the human leukocyte antigen region and survival of Chinese patients with non-small cell lung carcinoma
作者： Lei Cheng , Qi Liu , Mengyun Wang , Yanzi Gu , Jialei Wang
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摘要: Human leukocyte antigen (HLA) is highly polymorphic, driving presentation, complement cascade and maturation against cancer cells. Therefore, we extracted genotyping data in the HLA region from an ongoing Chinese genome-wide association study of non-small cell lung (NSCLC). Using deep sequencing 10 689 healthy Han Chinese, imputed for untyped genetic variants region, followed by a two-stage survival analysis 1531 NSCLC patients. In discovery stage 758 patients, identified 301 out 15 138 single-nucleotide polymorphisms to be independently associated with overall [P A rs6457642 C>T were hazards ratio 1.26 [95% confidence interval (CI) = 1.14-1.40 P 4.04 × 10-6] 0.76 (95% CI 0.66-0.87 1.16 10-4), respectively. The publically available ChIP-sequencing Hi-C found that rs241424 locus was involved potential cis-regulatory element long-range interaction HLA-DQA1 promoter. Additional expression quantitative trait loci showed G>A change decreased mRNA expression. Furthermore, levels lower tissues than adjacent normal tissues, worse prognosis patients adenocarcinoma. Collectively, may modulate OS possibly via mechanism promoter regulating
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