CAJ | 학술논문

目的探讨SMAD4基因单核苷酸多态性(SNPs)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438例煤工尘肺患者为病例组,448例同单位、同工种、工龄接近、无尘肺的煤尘接触者为对照组,进行统一的问卷调查;拍摄高仟伏X线后前位胸片;采集外周静脉血,酚-氯仿法提取DNA;根据中国人群HapMap database数据库查找SNP位点,多聚酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测SMAD4 6个SNPs位点的基因型.结果 6个SNPs位点的基因型分布频率中,仅SMAD4(rs10502913)病例组和对照组各基因型分布频率比较,差异有统计学意义(x2=6.512,P=0.038).携带SMAD4(rs10502913)AA基因型者发生煤工尘肺的危险性明显增高(调整后OR=1.63,95%CI=1.00～2.69,P=0.05);以是否吸烟为分层分析显示,携带SMAD4(rs10502913)AG基因型的不吸烟者发生煤工尘肺的危险性降低(调整后OR=0.54,95%CI=0.37～0.78,P＜0.01),而携带SMAD4(rs10502913)AG、AA基因型的吸烟者发生煤工尘肺危险性均增高(AG调整后OR=1.59,95%CI=1.01～2.50,P＜0.05;AA调整后OR=2.28,95%CI=1.09～4.80,P＜0.05);以煤工尘肺分期为分层分析显示,Ⅰ期尘肺组携带SMAD4(rs10502913)AA基因型者发生尘肺的危险性是携带GG型的2.42倍(调整后OR=2.42,95%CI=1.41～4.14,P＜0.01).携带SMAD4(rs9304407)GG基因型者煤工尘肺患病危险性与CC基因型比较明显降低(调整后OR=0.65,95%CI=0.43～0.98,P＜0.05);以是否吸烟为分层分析显示,不吸烟携带SMAD4(rs9304407)GC、GG基因型者发生煤工尘肺危险性明显降低(GC基因型调整后OR=0.60,95%CI=0.36～1.00,P＜0.05;GG基因型调整后OR=0.43,95%CI=0.25～0.74,P＜0.01).结论 SMAD4(rs10502913)位点AA基因型增加了煤工尘肺的危险性,SMAD4(rs9304407)位点GG基因型可能在尘肺的发生发展中起保护性作用.
목적 탐토SMAD4기인단핵감산다태성(SNPs)여매공진폐역감성적관계.방법 채용병례-대조적연구방법,선택438례매공진폐환자위병례조,448례동단위、동공충、공령접근、무진폐적매진접촉자위대조조,진행통일적문권조사;박섭고천복X선후전위흉편;채집외주정맥혈,분-록방법제취DNA;근거중국인군HapMap database수거고사조SNP위점,다취매련반응-한제성편단장도다태성(PCR-RFLP)방법검측SMAD4 6개SNPs위점적기인형.결과 6개SNPs위점적기인형분포빈솔중,부SMAD4(rs10502913)병례조화대조조각기인형분포빈솔비교,차이유통계학의의(x2=6.512,P=0.038).휴대SMAD4(rs10502913)AA기인형자발생매공진폐적위험성명현증고(조정후OR=1.63,95%CI=1.00～2.69,P=0.05);이시부흡연위분층분석현시,휴대SMAD4(rs10502913)AG기인형적불흡연자발생매공진폐적위험성강저(조정후OR=0.54,95%CI=0.37～0.78,P＜0.01),이휴대SMAD4(rs10502913)AG、AA기인형적흡연자발생매공진폐위험성균증고(AG조정후OR=1.59,95%CI=1.01～2.50,P＜0.05;AA조정후OR=2.28,95%CI=1.09～4.80,P＜0.05);이매공진폐분기위분층분석현시,Ⅰ기진폐조휴대SMAD4(rs10502913)AA기인형자발생진폐적위험성시휴대GG형적2.42배(조정후OR=2.42,95%CI=1.41～4.14,P＜0.01).휴대SMAD4(rs9304407)GG기인형자매공진폐환병위험성여CC기인형비교명현강저(조정후OR=0.65,95%CI=0.43～0.98,P＜0.05);이시부흡연위분층분석현시,불흡연휴대SMAD4(rs9304407)GC、GG기인형자발생매공진폐위험성명현강저(GC기인형조정후OR=0.60,95%CI=0.36～1.00,P＜0.05;GG기인형조정후OR=0.43,95%CI=0.25～0.74,P＜0.01).결론 SMAD4(rs10502913)위점AA기인형증가료매공진폐적위험성,SMAD4(rs9304407)위점GG기인형가능재진폐적발생발전중기보호성작용.
Objective To explore whether 6 tagging single nucleotide polymorphisms (SNPs) within SMAD4 gene were involved in the genetic susceptibility of coal worker's pneumoconiosis (CWP) by case-control study. Methods This study consisted of 438 CWP patients and 448 controls. All study subjects were Han Chinese, underground coal miners and recruited from coal mines of Xuzhou Mining Business Group Co Ltd.The 5 ml venous blood sample was obtained from all studied subjects and extracted genome DNA from the isolated leucocytes. Six SNPs were selected from the HapMap and detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Results The single SNP analyses showed that the genotype frequencies of SMAD4 (rs 10502913) was significantly different from those in controls (P＜0.05). Multivariate logistic regression analyses revealed that SMAD4 (rs10502913) AA genotype was associated with increased risk of CWP (adjusted OR=1.63,95%CI=1.00-2.69,P=0.05) and this was evident among subgroups of those smoker (adjusted OR =2.28,95% CI= 1.09～4.80, P＜0.05 ) and cases with stage Ⅰ (adjusted OR=2.42,95% CI=1.41～4.14,P＜0.01 ). The SMAD4 (rs9304407) GG genotype was associated with an decreased risk of CWP (adjusted OR=0.65,95%CI=0.43～0.98 ,P＜0.05 ) and the further stratification analysis showed that the risk of CWP was decreased in nonsmoking groups. Conclusions Our results suggest that individuals with the SMAD4(rs10502913) AA genotype was associated with an increased risk of CWP. However, carriers of SMAD4 (rs9304407) GG genotype have a protective effect on the developing CWP.