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Association of TLR and TREM-1 gene polymorphisms with risk of coronary artery disease in a Russian population
Authors:Alexey S. Golovkin  Anastasia V. Ponasenko  Maria V. Khutornaya  Anton G. Kutikhin  Ramil R. Salakhov  Arseniy E. Yuzhalin  Irina I. Zhidkova  Olga L. Barbarash  Leonid S. Barbarash
Affiliation:1. Research Institute for Complex Issues of Cardiovascular Diseases under the Siberian Branch of the Russian Academy of Medical Sciences, Kemerovo, Russian Federation;2. Central Research Laboratory, Kemerovo State Medical Academy, Kemerovo, Russian Federation;3. Department of Epidemiology, Kemerovo State Medical Academy, Kemerovo, Russian Federation;4. Department of Oncology, Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom
Abstract:Atherosclerosis, manifesting itself as acute coronary syndrome, stroke, and peripheral arterial diseases, is a chronic progressive inflammatory disease which is driven by responses of both innate and adaptive immunity. Toll-like receptors (TLRs) and Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) are important effectors of the innate immune system, and polymorphisms within genes encoding them may increase risk of occurrence of various pathologies including cardiovascular disorders. Thus, we carried out a genetic association study on the sample of 702 consecutive Caucasian (Russian) patients with coronary artery disease (CAD) and 300 age-, sex-, and ethnicity-matched healthy controls. We revealed that the C/C genotype of the TLR1 rs5743551 polymorphism was significantly associated with a reduced risk of CAD according to the recessive model (OR = 0.41, 95% CI = 0.20–0.84, P = 0.017, adjusted by age and gender). Concerning TREM-1 gene polymorphisms, we found that A/A genotype of the rs2234237 polymorphism, the G/G genotype of the rs6910730 polymorphism, the C/C genotype of the rs9471535 polymorphism, and the T/T genotype of the rs4711668 polymorphism were significantly associated with elevated CAD risk according to the recessive model (OR = 5.52, 95% CI = 1.17–25.98, P = 0.011; OR = 4.28, 95% CI = 1.09–16.81, P = 0.021; OR = 5.55, 95% CI = 1.18–26.09, P = 0.011, and OR = 1.66, 95% CI = 1.10–2.52, P = 0.014, respectively, adjusted by age and gender). Conversely, the G allele of the rs1817537 polymorphism, the T allele of the rs2234246 polymorphism, and the T allele of the rs3804277 polymorphism significantly correlated with similarly decreased risk of CAD according to the dominant model (OR = 0.57, 95% CI = 0.40–0.81, P = 0.0013; OR = 0.59, 95% CI = 0.42–0.84, P = 0.003, and OR = 0.58, 95% CI = 0.41–0.81, P = 0.0014, respectively, adjusted by age and gender). We conclude that certain TLR and TREM-1 gene polymorphisms may be associated with CAD in Russian population; however, their significance as predictive and pathogenic markers of CAD should be interpreted with caution in other populations.
Keywords:TLRs, Toll-like receptors   TREM, Triggering Receptor Expressed on Myeloid Cells   CAD, coronary artery disease   OR, odds ratio   95%CI, 95% confidence interval   SNPs, single nucleotide polymorphisms   IL, interleukin   TNF, tumor necrosis factor   CABG, coronary artery bypass graft surgery   RSC, Russian Society of Cardiology   EDTA, ethylenediaminetetraacetic acid   HWE, Hardy&ndash  Weinberg equilibrium   AIC, Akaike information criterion   LD, linkage disequilibrium   MI, myocardial infarction   NOD, nucleotide-binding oligomerization domain
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