Association Between PD-1 Gene Polymorphisms And NSCLC In A Chinese Han Population

Objective: To investigate whether the single nucleotide polymorphisms, PD-1.1(rs36084323), PD-1.9(rs2227981), PD-1.1(rs2227982) in PD-1 gene are associated with NSCLC in Chinese Han population.Methods: Peripheral venous blood samples from NSCLC patients and healthy persons were used for extracting DNA. Specific primers targeting gene segments harboring the three polymorphisms of PD-1.1, PD-1.5, PD-1.9 were designed. Target gene fragments of DNA specimens were amplified using PCR. Polymerase chain reaction-restriction fragment length polymorphisms(PCR-RFLP) was used to detect the genotype of PD-1.5 and PD-1.9. Allele-specific amplification(ASA-PCR) was used to the genotyping of PD-1.1. SPSS software was used to analyze the difference of SNPs between the NSCLC and control groups, and descriptive statistics analysis was used to check the relationship between the SNPs and NSCLC.Results: The AA, GA, GG genotype frequency of PD-1.1 are 19.6%, 50.2%, 30.2% and 27.8%, 48.8%, 23.4% respectively in case group and control group.The OR of PD-1.1 for GG genotype in comparison to AA genotype is 1.255(95%CI 0.819-1.923,P=0.017), the OR of PD-1.1 for GA genotype in comparison to GG genotype is 1.828(95%CI 1.111-3.008,P=0.296). The CC, CT and TT genotype frequency of PD-1.5 are 53.9%, 40.8%, 5.3% and 59.0%, 38.5%, 2.5% respectively in case group and control group. The OR of PD-1.5 for TT genotype in comparison to CC genotype is 0.421(95%CI 0.151-1,171,P=0.114), the OR of PD-1.5 for CT genotype in comparison to CC genotype is 0.862(95%CI 0.600-1.240, P=0.460). The CC, CT, TT genotype frequency of PD-1.9 are 1.6%, 94.1%, 4.3% and 3.9%, 94.1%, 2.0% respectively in case group and control group. The OR of PD-1.9 for TT genotype in comparison to CC genotype is 0.179(95%CI 0.037-0.863, P=0.060), the OR of PD-1.9 for CT genotype in comparison to CC genotype is 0.399(95%CI 0.129-1.239, P=0.101). According to above analysis, PD-1.5 and PD-1.9 polymorphisms of PD-1 gene have no significant association between case group and control group(P>0.05). The frequency of the GC haplotype in PD1.1/PD-1.5 has showed association between case and health controls(P=0.0026). PD-1.1 GA genotype(P=0.001) and AA genotype(P=0.006) are associated with NSCLC pathological types, and GA genotype is related to lymph node metastasis(P=0.029); PD-1.5 TT genotype is associated with the primary tumor, lymph node metastasis and distant metastasis(P=0.021, 0.047, 0.005, respectively). PD-1.9 TT genotype has association with clinical stage(P=0.015).Conclusion: These two SNPs of PD-1, PD-1.5 and PD-1.9 showed no significant association with NSCLC in Chinese Han population, but the frequency of the GC haplotype in PD-1.5/PD-1.9 has shown association between NSCLC and normal controls. PD-1.1 has shown significant association between cases and controls.