OBJECTIVES: Smoking behavior and genetic variations are important factors for the development of Crohn's disease (CD), but studies investigating the interaction between smoking and genetic background are scarce. We studied allelic associations of 19 confirmed variants located in 14 CD-associated genes or loci, in CD patients stratified for active smoking at diagnosis and passive smoking in childhood. METHODS: Genotyping data of 19 CD-associated single-nucleotide polymorphisms (SNPs) were available for 310 CD patients and 976 controls. Data on active smoking at diagnosis and passive smoking in childhood were obtained through a written questionnaire and a review of medical charts. RESULTS: The loci associated in smoking, but not in non-smoking, CD patients were 5p13.1 (rs17234657), DLG5 (rs2165047), NKX2-3 (rs10883365), and NOD2 (R702W). The loci associated in non-smoking, but not in smoking, CD patients were IL23R (rs7517847), 5p13.1 (rs9292777), IRGM (rs13361189 and rs4958847), IL12B (rs6887695), and CCNY (rs3936503). PTPN2 (rs2542151) was only associated in the smoking CD cohort (P=0.041), and not in the entire cohort (P=0.23) or in the non-smoking CD cohort (P=0.80). In passively smoking CD patients, associations with 13 SNPs in 9 loci were found, including PTPN2. In non-passive smoking CD patients, only associations with NOD2 (1007fsinsC and G908R) were found. CONCLUSIONS: The difference in associated genes between smoking and non-smoking CD patients implies a complex gene-environment interaction. Therefore, genetic studies of CD should be stratified for smoking behavior, as otherwise moderately associated genes such as PTPN2 can be missed.
OBJECTIVES: Smoking behavior and genetic variations are important factors for the development of Crohn's disease (CD), but studies investigating the interaction between smoking and genetic background are scarce. We studied allelic associations of 19 confirmed variants located in 14 CD-associated genes or loci, in CDpatients stratified for active smoking at diagnosis and passive smoking in childhood. METHODS: Genotyping data of 19 CD-associated single-nucleotide polymorphisms (SNPs) were available for 310 CDpatients and 976 controls. Data on active smoking at diagnosis and passive smoking in childhood were obtained through a written questionnaire and a review of medical charts. RESULTS: The loci associated in smoking, but not in non-smoking, CDpatients were 5p13.1 (rs17234657), DLG5 (rs2165047), NKX2-3 (rs10883365), and NOD2 (R702W). The loci associated in non-smoking, but not in smoking, CDpatients were IL23R (rs7517847), 5p13.1 (rs9292777), IRGM (rs13361189 and rs4958847), IL12B (rs6887695), and CCNY (rs3936503). PTPN2 (rs2542151) was only associated in the smoking CD cohort (P=0.041), and not in the entire cohort (P=0.23) or in the non-smoking CD cohort (P=0.80). In passively smoking CDpatients, associations with 13 SNPs in 9 loci were found, including PTPN2. In non-passive smoking CDpatients, only associations with NOD2 (1007fsinsC and G908R) were found. CONCLUSIONS: The difference in associated genes between smoking and non-smoking CDpatients implies a complex gene-environment interaction. Therefore, genetic studies of CD should be stratified for smoking behavior, as otherwise moderately associated genes such as PTPN2 can be missed.
Authors: Manuel Alvarez-Lobos; Daniela P Pizarro; Christian E Palavecino; Abner Espinoza; Valentina P Sebastián; Juan C Alvarado; Patricio Ibañez; Carlos Quintana; Orlando Díaz; Alexis M Kalergis; Susan M Bueno Journal: World J Gastroenterol Date: 2013-09-21 Impact factor: 5.742
Authors: Nora Meggyesi; Lajos S Kiss; Magdalena Koszarska; Martin Bortlik; Dana Duricova; Laszlo Lakatos; Tamas Molnar; Martin Leniček; Libor Vítek; Istvan Altorjay; Maria Papp; Zsolt Tulassay; Pal Miheller; Janos Papp; Attila Tordai; Hajnalka Andrikovics; Milan Lukas; Peter Laszlo Lakatos Journal: World J Gastroenterol Date: 2010-11-07 Impact factor: 5.742
Authors: Govind K Makharia; Balakrishnan S Ramakrishna; Philip Abraham; Gourdas Choudhuri; Sri Prakash Misra; Vineet Ahuja; Shobna J Bhatia; Deepak K Bhasin; Sunil Dadhich; Gopal K Dhali; Devendra C Desai; Uday C Ghoshal; B D Goswami; Sanjeev K Issar; Ajay K Jain; Venkataraman Jayanthi; Goundappa Loganathan; C Ganesh Pai; Amarender S Puri; Surinder S Rana; Gautam Ray; Shivaram P Singh; Ajit Sood Journal: Indian J Gastroenterol Date: 2012-10-17