title: Genetic polymorphisms of molecules associated with inflammation and immune response in Japanese subjects with functional dyspepsia.
abstract: Inflammatory changes in the gastric mucosa are commonly observed in Japanese patients with functional dyspepsia (FD). However, detailed data regarding the relationship between the genetic regulatory factors of inflammation and FD are not available. We investigated the associations between FD and genetic polymorphisms of molecules associated with inflammation or immune response (IL-17A, -17F and MIF). The study was performed with 278 subjects (188 with no upper abdominal symptoms and 90 with FD according to the Roma III criteria). We employed the PCR-SSCP (multiplex PCR for IL-17A and -17F) method to detect the gene polymorphisms. Overall, the polymorphisms of the IL-17A, -17F and MIF genes were not correlated with the susceptibility to FD. However, the MIF -173C allele carrier had a significantly increased risk for the development of epigastric pain syndrome (EPS) of FD (OR, 2.12; 95% CI, 1.00-4.49; p=0.0497). In Helicobacter pylori (H. pylori)-infected cases, the number of IL-17F 7488T alleles was positively correlated with the development of EPS (OR, 11.3; 95% CI, 1.23-103.2; p=0.032), while the IL-17F T/T homozygote and the MIF -173C carrier had an increased risk for EPS (OR, 10.4; 95% CI, 1.17-92.3; p=0.036 and OR, 3.66; 95% CI, 1.19-11.3; p=0.024, respectively). In addition, a significant interaction between the IL-17F 7488 polymorphism and H. pylori infection was shown to increase the activity and inflammation scores (p=0.043 and 0.042, respectively). There were no significant associations between the IL-17A polymorphism and FD. Our results provide the first evidence that the IL-17F and MIF gene polymorphisms are significantly associated with the development of FD, particularly EPS, a subgroup of FD, in H. pylori-infected subjects. The genetic polymorphisms of inflammation or immune response-related molecules are involved in the development of one of the FD subgroups via H. pylori-induced gastric inflammation.
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake 470-1192, Japan. tarisawa@fujita-hu.ac.jp
authors.forename: Tomiyasu
authors.initials: T
authors.lastname: Arisawa
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Tahara
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nagasaka
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kamiya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujita
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yoshioka
authors.forename: Yuko
authors.initials: Y
authors.lastname: Arima
authors.forename: Masaaki
authors.initials: M
authors.lastname: Okubo
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakano
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D044466:Asian People / Q000235:genetics; D002465:Cell Movement; D004415:Dyspepsia / Q000150:complications / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications / Q000235:genetics; D006801:Humans; D007249:Inflammation; D020381:Interleukin-17 / Q000235:genetics*; D007564:Japan; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: C440021:IL17F protein, human; D020381:Interleukin-17; D008263:Macrophage Migration-Inhibitory Factors