{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:25:53Z","timestamp":1791120353331,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2010,7,1]],"date-time":"2010-07-01T00:00:00Z","timestamp":1277942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2010,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Glutathione S\u2010transferase (GST) genes as well as heme oxygenase 1 gene (HMOX1) encode enzymes that detoxify carcinogens and protect against oxidative stress. This study was undertaken to examine the impact of gene\u2013smoking interactions on susceptibility to rheumatoid arthritis (RA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Caucasian patients with RA and matched control subjects (n = 549 each) were selected from the Nurses' Health Study. Genotyping of the patients' blood by TaqMan and BioTrove assays identified homozygous deletions at the M1 and T1 loci of GST (GSTM1\u2010null and GSTT1\u2010null, respectively) as well as alleles for GSTP1 (rs1695) and HMOX1 (rs2071746). In addition, the effect of gene\u2013smoking interactions on the risk of all RA and RA serologic phenotypes was studied in separate logistic models that were adjusted for covariates. Multiplicative interactions were assessed by including a product term in a logistic model, and additive interactions were assessed using the attributable proportion (AP) due to interaction. For replication of the results, analyses revealing significant interactions were repeated in an independent case\u2013control cohort from the Epidemiological Investigation of Rheumatoid Arthritis study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>For the risk of all RA, multiplicative (<jats:italic>P<\/jats:italic> = 0.05) and additive (AP = 0.53, <jats:italic>P<\/jats:italic> = 0.0005) interactions between the GSTT1\u2010null polymorphism and smoking and multiplicative interactions (<jats:italic>P<\/jats:italic> = 0.05) between HMOX1 and smoking were observed. For the risk of seropositive RA, multiplicative (<jats:italic>P<\/jats:italic> = 0.01) and additive (AP = 0.62, <jats:italic>P<\/jats:italic> &lt; 0.0001) interactions between GSTT1\u2010null and smoking and additive interactions (AP = 0.41, <jats:italic>P<\/jats:italic> = 0.03) between HMOX1 and smoking were observed. After correction for multiple comparisons, the additive interactions between GSTT1\u2010null and smoking remained significant. The M1\u2010null and P1 variants of GST did not show significant interactions, and no associations with seronegative RA were observed. In replication analyses, significant multiplicative interactions (<jats:italic>P<\/jats:italic> = 0.04) and additive interactions (AP = 0.32, <jats:italic>P<\/jats:italic> = 0.02) were observed between GSTT1\u2010null and smoking in the risk of anti\u2013citrullinated protein antibody\u2013positive RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Significant gene\u2013environment interactions between the GSTT1\u2010null polymorphism and heavy smoking were observed when assessing the risk of RA. Future studies are needed to assess the impact of these interactions on RA prediction.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.27639","type":"journal-article","created":{"date-parts":[[2010,7,6]],"date-time":"2010-07-06T19:34:54Z","timestamp":1278444894000},"page":"3196-3210","source":"Crossref","is-referenced-by-count":43,"title":["Effect of interactions of glutathione S\u2010transferase T1, M1, and P1 and HMOX1 gene promoter polymorphisms with heavy smoking on the risk of rheumatoid arthritis"],"prefix":"10.1002","volume":"62","author":[{"given":"Brendan T.","family":"Keenan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori B.","family":"Chibnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonid","family":"Padyukov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Kallberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Bengtsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Klareskog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Alfredsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth W.","family":"Karlson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,10,29]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199904)42:3<415::AID-ANR4>3.0.CO;2-Z"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2005.09.053"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(02)01051-3"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.62.9.835"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199905)42:5<910::AID-ANR9>3.0.CO;2-D"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.102962"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780301102"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000024"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21575"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20553"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22597"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1086\/516736"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1383-5742(00)00050-8"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1159\/000028396"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4274(99)00230-1"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(01)00206-8"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwm383"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwn417"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwj321"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.15.10004"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1994.00893.x"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwf018"},{"key":"e_1_2_7_24_2","first-page":"733","article-title":"Molecular epidemiology of the human glutathione S\u2010transferase genotypes GSTM1 and GSTT1 in cancer susceptibility","volume":"6","author":"Rebbeck TR","year":"1997","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_7_25_2","first-page":"229","article-title":"Genetic polymorphisms of glutathione S\u2010transferases and disease activity of rheumatoid arthritis","volume":"27","author":"Bohanec Grabar P","year":"2009","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.58.3.164"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10174"},{"key":"e_1_2_7_28_2","first-page":"992","article-title":"Glutathione S\u2010transferase M1, T1, and P1 genotypes and rheumatoid arthritis","volume":"32","author":"Yun BR","year":"2005","journal-title":"J Rheumatol"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(03)00181-9"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.2.10.3290025"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2005.00804.x"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2004.07.008"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.55.3.5"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-004-1162-2"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21754"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23048"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23970"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00051793"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/1047-2797(94)00096-C"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20621"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.2144\/03353dd02"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a112335"},{"key":"e_1_2_7_44_2","first-page":"655","article-title":"A SAS program calculating three measures of interaction with confidence intervals","volume":"7","author":"Lundberg M","year":"1996","journal-title":"Epidemiology"},{"key":"e_1_2_7_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-005-7835-x"},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-199209000-00012"},{"key":"e_1_2_7_47_2","first-page":"2290","article-title":"Mach 1.0: rapid haplotype reconstruction and missing genotype inference","volume":"79","author":"Li Y","year":"2006","journal-title":"Am J Hum Genet"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.3109\/00498259309059411"},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.049338"},{"key":"e_1_2_7_50_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar2421"},{"key":"e_1_2_7_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng2075"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.27639","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.27639","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T17:13:09Z","timestamp":1697044389000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.27639"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,10,29]]},"references-count":50,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2010,11]]}},"alternative-id":["10.1002\/art.27639"],"URL":"https:\/\/doi.org\/10.1002\/art.27639","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,10,29]]}}}