CAJ | 학술논문

目的探讨凋亡信号通路基因细胞凋亡基因(FAS)、FAS配体基因(FASL)、半胱氨酸-天冬氨酸蛋白质酶(CASP8)及CASP3单核苷酸多态性(SNP)与煤工尘肺易感性的关系.方法采用病例-对照的研究方法,选择511例煤工尘肺患者为病例组,530例同单位、同工种、且工龄相近、未患尘肺的煤尘接触者为对照组；聚合酶链反应-限制性片段长度多态性( PCR-RFLP)法检测5个SNP位点的基因型；CASP3 rs 6948位点用荧光定量PCR法进行基因分型.结果煤工尘肺组和对照组6个多态性位点的各基因型的分布频率比较,差异无统计学意义(P＞0.05).CASP8-652位点的6个碱基缺失(DD型)可明显增加煤工尘肺患病的危险性(调整后OR=1.96,95％ CI=1.15～3.33,P=0.013),其他各基因型对煤工尘肺患病危险性没有明显的影响；对CASP8-652 I＞D基因多态性进行分层分析发现,工龄≥28年组、吸烟组及1期煤工尘肺携带CASP8-652 DD基因型者煤工尘肺的患病危险性明显增高,差异有统计学意义(P＜0.05).6个多态性位点不同基因型之间的相互作用与煤工尘肺患病的关联性分析发现,携带FAS-1377GG/CASP8-652DD型者、携带FAS-670AG/CASP8-652DD型者和携带FASL-844CT/CASP8-652DD型者煤工尘肺患病危险性明显增加；携带FAS- 1377GA/CASP8-652ID型者煤工尘肺患病危险性明显降低.对Ⅰ期煤工尘肺患者中CASP8-652位点II、ID、DD 3种基因型携带者发病前的粉尘暴露时间进行回归分析,差异无统计学意义(P＞0.05).Ⅰ期煤工尘肺患者中不同基因型携带者发病前的粉尘暴露时间比较,差异无统计学意义(P＞0.05).结论 CASP8-652缺失基因型在煤工尘肺病变的发展过程中可能起一定的作用,并且与FAS- 1377、FAS-670及FAL-844存在基因相互作用.
목적 탐토조망신호통로기인세포조망기인(FAS)、FAS배체기인(FASL)、반광안산-천동안산단백질매(CASP8)급CASP3단핵감산다태성(SNP)여매공진폐역감성적관계.방법 채용병례-대조적연구방법,선택511례매공진폐환자위병례조,530례동단위、동공충、차공령상근、미환진폐적매진접촉자위대조조；취합매련반응-한제성편단장도다태성( PCR-RFLP)법검측5개SNP위점적기인형；CASP3 rs 6948위점용형광정량PCR법진행기인분형.결과 매공진폐조화대조조6개다태성위점적각기인형적분포빈솔비교,차이무통계학의의(P＞0.05).CASP8-652위점적6개감기결실(DD형)가명현증가매공진폐환병적위험성(조정후OR=1.96,95％ CI=1.15～3.33,P=0.013),기타각기인형대매공진폐환병위험성몰유명현적영향；대CASP8-652 I＞D기인다태성진행분층분석발현,공령≥28년조、흡연조급1기매공진폐휴대CASP8-652 DD기인형자매공진폐적환병위험성명현증고,차이유통계학의의(P＜0.05).6개다태성위점불동기인형지간적상호작용여매공진폐환병적관련성분석발현,휴대FAS-1377GG/CASP8-652DD형자、휴대FAS-670AG/CASP8-652DD형자화휴대FASL-844CT/CASP8-652DD형자매공진폐환병위험성명현증가；휴대FAS- 1377GA/CASP8-652ID형자매공진폐환병위험성명현강저.대Ⅰ기매공진폐환자중CASP8-652위점II、ID、DD 3충기인형휴대자발병전적분진폭로시간진행회귀분석,차이무통계학의의(P＞0.05).Ⅰ기매공진폐환자중불동기인형휴대자발병전적분진폭로시간비교,차이무통계학의의(P＞0.05).결론 CASP8-652결실기인형재매공진폐병변적발전과정중가능기일정적작용,병차여FAS- 1377、FAS-670급FAL-844존재기인상호작용.
Objective To explore the possible association between six single nucleotide polymorphisms (SNPs) of Fas pathway genes and the risks of coal worker pneumoconiosis (GWP).Methods This casecontrol study consisted of 511 male patients with CWP and 530 male controls from the same coal mines.Five SNPs of Fas pathway genes were detected by restriction fragment length polymorphisms (PCR-RFLP) and CASP3 (rs6948) was genotyped by quantitative real-time polymerase chain reaction (qRT-PCR).Results There were no differences of genotype frequencies of 6 SNPs between cases with CWP and controls.A significant increased risk of CWP was found in subjects with CASP8-652DD genotype as compared to subjects with CASP8-652II genotype (P＜0.05),and the further stratification analysis showed that smoking cases with CWP stage Ⅰ,long exposure time and CASP8-652DD genotype had high risk of CWP (P＜0.05).The analysis of gene-gene interactions indicated that the carriers with FAS-1377GG/ CASP8-652DD,FAS-670AG/CASP8-652DD and FASL-844CT/CASP8-652DD had the increased risk of CWP,and the carriers with FAS-1377GA/CASP8-652ID had the reduced risk of CWP.There were no significant differences of exposure times among the cases with CWP stage Ⅰ and 3 genotypes of CASP8-652.Conclusion CASP8-652 6N DD genotype may play a role in CWP development and interact with SNPs of FAS-1377 、FAS-670 and FASL-844.