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PLoS One. 2017 Jan 3;12(1):e0168828. doi: 10.1371/journal.pone.0168828. eCollection 2017.

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.

Author information

1
Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
2
Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, México.
3
Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
4
Histocompatibility Laboratory, Research Unit, Hospital Juárez de México, Mexico City, Mexico.
5
Cardiovascular Genomics Laboratory, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.

Abstract

AIM:

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.

CONCLUSION:

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.

PMID:
28045954
PMCID:
PMC5207498
DOI:
10.1371/journal.pone.0168828
[Indexed for MEDLINE]
Free PMC Article

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