Effect of interactions of glutathione S-transferase T1, M1, and P1 and HMOX1 gene promoter polymorphisms with heavy smoking on the risk of rheumatoid arthritis.
Effect of interactions of glutathione S-transferase T1, M1, and P1 and HMOX1 gene promoter polymorphisms with heavy smoking on the risk of rheumatoid arthritis.
复制标题
DOI：
10.1002/art.27639
复制
发表时间：
2010-11
影响因子：
--
通讯作者：
Karlson, Elizabeth W.
中科院分区：
文献类型：
--
作者：
Keenan, Brendan T.;Chibnik, Lori B.;Cui, Jing;Ding, Bo;Padyukov, Leonid;Kallberg, Henrik;Bengtsson, Camilla;Klareskog, Lars;Alfredsson, Lars;Karlson, Elizabeth W.
谷胱甘肽S-转移酶（GST）和血红素加氧酶-1（HMOX 1）基因编码的酶可以解毒致癌物质并保护免受氧化应激。我们研究了基因吸烟相互作用对类风湿性关节炎（RA）的易感性。从护士健康研究中选择了549例匹配的白人RA病例和对照。TaqMan和BioTrove基因分型分别鉴定出GSTM 1、GSTT 1纯合缺失（null）和GSTP 1（rs 1695）、HMOX 1（rs 2071746）等位基因。我们研究了基因吸烟的相互作用对所有RA和血清学RA表型的风险，在单独的logistic模型调整协变量。我们评估了逻辑模型中与产品项的乘法相互作用和与归因于相互作用的比例（AP）的加法相互作用。为了重复，我们在一个独立的病例对照样本中重复了显著性分析，该样本来自RA的流行病学调查。对于所有RA风险，我们观察到：GSTT 1-null和吸烟之间的乘法（p=0.05）和加法（AP=0.53，p=0.0005）相互作用以及HMOX 1和吸烟之间的乘法相互作用（p=0.05）。对于血清阳性的RA风险，我们发现GSTT 1-null和吸烟之间的乘法（p=0.01）和加法（AP=0.63，p<0.0001）相互作用以及HMOX 1和吸烟之间的加法相互作用（AP=0.41，p=0.03）。多重比较校正后，添加剂的相互作用GSTT 1-null和吸烟仍然显着。GSTM 1-null和GSTP 1没有显示出显著的相互作用。未观察到与血清阴性RA相关。在重复分析中，我们观察到ACPA阳性RA风险的GSTT 1-null和吸烟之间存在显著的乘法（p=0.04）和加法（AP=0.32，p=0.02）相互作用。我们观察到GSTT 1-null和重度吸烟对RA风险的显着基因-环境相互作用。未来的研究需要评估这些相互作用对RA预测的影响。
Glutathione S-transferase (GST) and heme oxygenase-1 (HMOX1) genes encode enzymes that detoxify carcinogens and protect against oxidative stress. We studied gene-smoking interactions on rheumatoid arthritis (RA) susceptibility. 549 matched Caucasian RA cases and controls were selected from the Nurses' Health Study. Genotyping by TaqMan and BioTrove identified GSTM1, GSTT1 homozygous deletions (null) and GSTP1 (rs1695), HMOX1 (rs2071746) alleles, respectively. We studied gene-smoking interactions on the risk of all RA and serologic RA phenotypes in separate logistic models adjusted for covariates. We assessed multiplicative interactions with product terms in the logistic models and additive interactions with the attributable proportion due to interaction (AP). For replication, we repeated significant analyses in an independent case-control sample from the Epidemiologic Investigation of RA. For all RA risk, we observed: multiplicative (p=0.05) and additive (AP=0.53, p=0.0005) interactions between GSTT1-null and smoking and multiplicative interaction (p=0.05) between HMOX1 and smoking. For seropositive RA risk, we found multiplicative (p=0.01) and additive (AP=0.63, p<0.0001) interactions between GSTT1-null and smoking and additive interaction (AP=0.41, p=0.03) between HMOX1 and smoking. After correction for multiple comparisons, additive interactions for GSTT1-null and smoking remained significant. GSTM1-null and GSTP1 did not show significant interactions. No associations were seen with seronegative RA. In replication analyses, we observed significant multiplicative (p=0.04) and additive (AP=0.32, p=0.02) interactions between GSTT1-null and smoking for ACPA-positive RA risk. We observed significant gene-environment interactions between GSTT1-null and heavy smoking on RA risk. Future studies are needed to assess the impact of these interactions on RA prediction.
登录
查看更多内容
影响因子：
9.8
作者：
Kallberg, Henrik;Padyukov, Leonid;Alfredsson, Lars
通讯作者：
Alfredsson, Lars
影响因子：
13.6
作者：
Andersson, T;Alfredsson, L;Ahlbom, A
通讯作者：
Ahlbom, A
影响因子：
2.7
作者：
Covault, J;Abreu, C;Oncken, C
通讯作者：
Oncken, C
影响因子：
27.4
作者：
Karlson EW;Chang SC;Cui J;Chibnik LB;Fraser PA;De Vivo I;Costenbader KH
通讯作者：
Costenbader KH
影响因子：
4.5
作者：
Fernando MM;Stevens CR;Walsh EC;De Jager PL;Goyette P;Plenge RM;Vyse TJ;Rioux JD
通讯作者：
Rioux JD