title: The rs7044343 Polymorphism of the Interleukin 33 Gene Is Associated with Decreased Risk of Developing Premature Coronary Artery Disease and Central Obesity, and Could Be Involved in Regulating the Production of IL-33.
abstract: OBJECTIVE
  The effect of interleukin 33 (IL-33) in the inflammatory process generates significant interest in the potential significance of IL-33 as a biomarker for coronary artery disease (CAD). Here, our objective was to analyze whether IL-33 gene polymorphisms are associated with premature CAD in a case-control association study.
  
  
  METHODS
  Four IL-33 polymorphisms (rs7848215, rs16924144, rs16924159 and rs7044343) were genotyped by 5' exonuclease TaqMan assays in 1095 patients with premature CAD and 1118 controls.
  
  
  RESULTS
  The rs7044343 T allele was significantly associated with a diminished risk of premature CAD (OR = 0.81, 95% CI: 0.69-0.97, Pdom = 0.020; OR = 0.85, 95% CI: 0.75-0.96, Padd = 0.019) and central obesity (OR = 0.74, 95% CI: 0.58-0.93, Pdom = 0.0007), respectively. When patients were divided into groups with and without type 2 diabetes mellitus (T2DM), the rs7044343 T allele was associated with a reduced risk of premature CAD in patients without (OR = 0.85, 95% CI: 0.73-0.99, Padd = 0.038) and with T2DM (OR = 0.61, 95% CI: 0.38-0.97, Pdom = 0.039; OR = 0.69, 95% CI: 0.49-0.97, Padd = 0.035). In order to establish the functional effect of the rs7044343 polymorphism, the production of IL-33 was determined in monocytes of selected individuals. Monocytes from individuals with rs7044343 CC genotype produced higher levels of IL-33 than monocytes from individuals with other genotypes.
  
  
  CONCLUSIONS
  The results suggest that the IL-33 rs7044343 T allele could be a susceptibility marker for premature CAD and central obesity. The rs7044343 polymorphism could be involved in regulating the production of IL-33.
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: Javier
authors.initials: J
authors.lastname: Angeles-Martínez
authors.affiliation: Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, México.
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Posadas-Sánchez
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: Luis
authors.initials: L
authors.lastname: Llorente
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: Edith
authors.initials: E
authors.lastname: Alvarez-León
authors.affiliation: Histocompatibility Laboratory, Research Unit, Hospital Juárez de México, Mexico City, Mexico.
authors.forename: Julian
authors.initials: J
authors.lastname: Ramírez-Bello
authors.affiliation: Cardiovascular Genomics Laboratory, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.
authors.forename: Teresa
authors.initials: T
authors.lastname: Villarreal-Molina
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Lima
authors.affiliation: Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, México.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Cardoso-Saldaña
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Rodríguez-Pérez
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: Nonanzit
authors.initials: N
authors.lastname: Pérez-Hernández
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Fragoso
authors.affiliation: Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, México.
authors.forename: Carlos
authors.initials: C
authors.lastname: Posadas-Romero
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: Gilberto
authors.identifier: http://orcid.org/0000-0001-7916-5163
authors.initials: G
authors.lastname: Vargas-Alarcón
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation; D000067596:Interleukin-33 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D056128:Obesity, Abdominal / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D014057:Tomography, X-Ray Computed
chemical_list: D005819:Genetic Markers; C506536:IL33 protein, human; D000067596:Interleukin-33