| Objectives A genome-wide association study and candidate genes association analysis showed that some genes were associated with pulmonary fibrosis recently,including desmoplakin(DSP),family with sequence similarity 13 member A(FAM13A),dipeptidylpeptidase 9(DPP9)and telomerase reverse transcriptase(TERT),telomerase RNA component(TERC),nuclear assembly factor 1(NAF1)and cytochrome b245 alpha(CYBA).This study was designed to investigate the association between single nucleotide polymorphism of 7 candidate genes with CWP,and provided a theoretical basis for early screening of risk-population and study of genetic mechanism of CWP.Methods A case-control study was designed in this study.we genotyped 16 SNP loci in652 CWP patients and 648 dust control subjects by using matrix-assisted laser desorption/ionization time of flight mass spectrometry.The frequency of genotypes distribution and alleles distribution,and genetic models of SNP loci were analyzed by PLink1.07 software,including additive genetic model,dominant genetic model and recessive genetic model.Linkage disequilibrium analysis and haplotypes formed by SHEsis software.Data were analyzed using SPSS17.0 software package.P values less than 0.05 was considered as significant difference.Results 1 Chi square test showed that the frequencies of genotypes and alleles of TERT rs2736100,NAF1(rs4691896 and rs3822304),and CYBA rs7195830 bet ween the CWP group and the dust control group were significantly different(P<0.05).The C allele frequency of TERT rs2736100 was lower in CWP group than in dust control group(OR=0.840,95%CI=0.717-0.984,P=0.031).The frequencies of rs4691896 T allele and rs3822304 G allele of NAF1 gene were higher in CWP gro up than in control group(OR=1.891,95%CI=1.536-2.330,P<0.001;OR=1.9622,95%CI=1.167-3.300,P=0.010).Similarly,the A allele frequency of CYBA rs7195830 was significantly higher in CWP group than in dust control group(OR=1.550,95%CI=1.289-1.863,P<0.001).There were no significant difference were founded in th e distribution frequencies of genotypes and alleles on DSP rs2076295 and CYBA(rs13306296,rs4673,rs9932581 and rs16966671)and TERC(rs10936599 and rs12696304)and NAF1(rs7675998,rs12331717 and rs936562),DPP9 rs12610495 and FAM13 A rs2609255 between CWP group and dust control group(P>0.05).2 Gen etic model test observed that TERT rs2736100 and NAF1 rs3822304 were contrib uted to CWP in additive genetic model(OR=0.844,95%CI=0.722-0.987,P=0.034;OR=1.959,95%CI=1.164-3.295,P=0.011).NAF1 rs4691896 was contributed to C WP in the additive genetic model and dominant genetic model(OR=1.961,95%CI=1.579-2.436,P<0.001;OR=1.671,95%CI=1.142-2.442,P=0.008).CYBA rs7195830 was related to CWP in the additive genetic model and dominant genetic model(O R=1.621,95%CI=1.334-1.970,P<0.001;OR=1.711,95%CI=1.197,P=0.003).There were no significant difference for the genotypic distributions on DSP rs2076295,CYBA(rs13306296,rs4673,rs9932581 and rs16966671),TERC(rs10936599 and r s12696304),NAF1(rs7675998,rs12331717 and rs936562),DPP9 rs12610495 and F AM13 A rs2609255 in additive model,dominant model and recessive model betwe en CWP group and dust control group(P>0.05).3 The haplotype test revealed that haplotypes ACA,ATA,GCT and GTA formed by rs7675998,rs4691896 and rs936562 of NAF1 gene.The frequency of haplotype ACA was lower in CWP group than in dust control group(0.2%vs5.7%,P<0.05).The frequencies of haplotypes ATA and GTA were higher in CWP group than in dust control group(17.5%,4.3%vs10.3%,2.5%,P<0.05).The frequency of haplotype GCT was not statistically significant between CWP group and dust control group(77.5%vs78.6%,P>0.05).Conclusions 1 TERT rs2736100,NAF1(rs4691896 and rs3822304)and CYBA rs7195830 loci are associated with CWP,TERT,NAF1 and CYBA gene may be the susceptibility genes in patients with CWP.2 Haplotypes ACA,ATA and GTA formed by rs7675998,rs4691896 and rs936562 loci of NAF1 gene are related to CWP. |
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