Genetic diversity and the structure of linkage disequilibrium in the methylenetetrahydrofolate reductase locus

Investigation of linkage disequilibrium block architecture in human genome is modern, intensely investigated field of molecular genetics. In the present study, genetic differentiation and linkage disequilibrium pattern in the methylenetetrahydrofolate reductase (MTHFR) locus was examined in the populations of Russians, Tuvinians, and Northern and Southern Kyrgyzes. Methylenetetrahydrofolate reductase is the key enzyme of folate cycle, responsible for reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. Decreased enzymatic activity of this protein often caused by certain associations of MTHFR alleles results in the increased plasma homocysteine levels. In the population groups examined, genotype and allele frequencies at five polymorphic MTHFR loci: rs17037397, rs4846052, rs1801133, rs1801131, and rs1537516 were evaluated. Statistically significant genetic differences between the population group of Southern Kyrgyzes and the other groups, as well as between Russians and Tuvinians, were demonstrated. In the MTHFR gene from the population of Southern Kyrgyzes one block was revealed; in the populations of Russians, Tuvinians, and Northern Kyrgyzes two blocks were detected. Thus, the structure of linkage disequilibrium in the MTHFR locus demonstrated population-specific pattern.     

Polymorphic variants in tenascin-C (TNC) are associated with atherosclerosis and coronary artery disease

Tenascin-C (TNC) is an extracellular matrix protein implicated in biological processes important for atherosclerotic plaque development and progression, including smooth muscle cell migration and proliferation. Previously, we observed differential expression of TNC in atherosclerotic aortas compared with healthy aortas. The goal of this study was to investigate whether common genetic variation within TNC is associated with risk of atherosclerosis and coronary artery disease (CAD) in three independent datasets. We genotyped 35 single nucleotide polymorphisms (SNPs), including 21 haplotype tagging SNPs, in two of these datasets: human aorta tissue samples (n?=?205) and the CATHGEN cardiovascular study (n?=?1,325). Eleven of these 35 SNPs were then genotyped in a third dataset, the GENECARD family study of early-onset CAD (n?=?879 families). Three SNPs representing a block of linkage disequilibrium, rs3789875, rs12347433, and rs4552883, were significantly associated with atherosclerosis in multiple datasets and demonstrated consistent, but suggestive, genetic effects in all analyses. In combined analysis rs3789875 and rs12347433 were statistically significant after Bonferroni correction for 35 comparisons, p?=?2?×?10^?6 and 5?×?10^?6, respectively. The SNP rs12347433 is a synonymous coding SNP and may be biologically relevant to the mechanism by which tenascin-C influences the pathophysiology of CAD and atherosclerosis. This is the first report of genetic association between polymorphisms in TNC and atherosclerosis or CAD.     

APOA1 gene polymorphisms in the South Asian immigrant population in the United States

BACKGROUND:

Coronary artery disease (CAD) is a leading cause of death in the United States. South Asian immigrants (SAIs) from the Indian subcontinent living in the US are disproportionately at higher risk of CAD than other immigrant populations. Unique genetic factors may predispose SAIs to increased risk of developing CAD when adopting a Western lifestyle including a higher-fat diet, more sedentary behavior and additional gene-environment interactions. SAIs are known to have low levels of the protective high density lipoprotein (HDL) and an altered function for Apo-lipoprotein A-1 (ApoA1), the main protein component of HDL cholesterol. One gene that may be genetically distinctive in this population is APOA1 which codes for ApoA-1 protein, a potentially important contributing factor in the development of CAD.

MATERIALS AND METHODS:

DNA sequencing was performed to determine the status of the seven single-nucleotide polymorphisms (SNPs) in the APOA1 gene from 94 unrelated SAI adults. Genotypes, allelic frequencies, and intragenic linkage disequilibrium of the APOA1 SNPs were calculated.

RESULTS:

Several polymorphisms and patterns were common among persons of south Asian ethnicity. Frequencies for SNPs T655C, T756C and T1001C were found to be different than those reported in European Caucasian individuals. Linkage disequilibrium was found to be present between most (13 of 15) SNP pairings indicating common inheritance patterns.

CONCLUSIONS:

SAIs showed variability in the sequence of the APOA1 gene and linkage disequilibrium for most SNPS. This pattern of APOA1 SNPs may contribute to decreased levels of HDL cholesterol reported in SAIs, leading to an increased risk for developing CAD in this population.     

Relationship between common eNOS gene polymorphisms and predisposition to coronary artery disease: Evidence from a meta-analysis of 155 published association studies

BackgroundRelationship between endothelial nitric oxide synthase (eNOS) polymorphisms and predisposition to coronary artery disease (CAD) are still controversial and ambiguous. So we performed this meta-analysis to more precisely estimate relationship between eNOS polymorphisms and CAD by pooling the results of already published studies.MethodsWe searched Pubmed, Embase, Web of Science and CNKI for eligible studies. We used Review Manager to pool the results of eligible studies.ResultsOne hundred and fifty-five studies were included in this meta-analysis. We found that eNOS rs1799983, rs2070744 and rs869109213 polymorphisms were all significantly associated with CAD in the general population. We also detected similar significant results for eNOS rs1799983, rs2070744 and rs869109213 polymorphisms in both Caucasians and Asians in further subgroup analyses.ConclusionsThis meta-analysis demonstrated that eNOS rs1799983, rs2070744 and rs869109213 polymorphisms might influence predisposition to CAD in both Caucasians and Asians.     

A meta-analysis on associations of FTO,MTHFR and TCF7L2 polymorphisms with polycystic ovary syndrome

BackgroundWe aimed to better clarify the relationship between FTO/MTHFR/TCF7L2 polymorphisms and PCOS in a larger combined population by performing a meta-analysis.MethodsEligible articles were retrieved from Pubmed, Embase, Web of Science and CNKI. Review Manager Version was used to perform statistical analyses.ResultsForty-six studies were included for this meta-analysis. FTO rs9939609 polymorphism was found to be significantly associated with PCOS under dominant, recessive, over-dominant and allele comparisons, MTHFR rs1801131 polymorphism was found to be significantly associated with PCOS under recessive and allele comparisons, and MTHFR rs1801133 polymorphism was also found to be significantly associated with PCOS under dominant, recessive and allele comparisons in general population. In subgroup analyses, we found that positive results were mainly driven by the Asians.ConclusionsCollectively, this meta-analysis proved that FTO rs9939609, MTHFR rs1801131 and MTHFR rs1801133 polymorphisms may serve as predisposing factors of PCOS, especially for Asians.     

Toll-like receptor 8 polymorphism and coronary artery disease

Toll-like receptors (TLRs) play roles in innate and adaptive immune responses. Some TLRs are involved in the pathogenesis of cardiovascular diseases. Coronary artery disease (CAD) has an inflammatory and immunological basis. We investigated whether TLR8 Met1Val and TLR8-129G>C single nucleotide polymorphisms (SNPs rs3764879 and rs3764880) are associated with CAD in the Chinese population. We enrolled 412 consecutive patients (185 with coronary stenosis ≥50% or previous myocardial infarction and 227 controls). Ligase detection reaction was performed to detect SNPs rs3764879 and rs3764880 of TLR8. The SNP at rs3764879 is in complete linkage disequilibrium with rs3764880. No significant difference was found in genotypic or allelic frequencies of these two common SNPs between CAD cases and controls (P > 0.05, respectively). No associations existed between these two SNPs and the severity of coronary artery stenosis (All P > 0.05). These results do not support an involvement of SNPs rs3764879 and rs3764880 of TLR8 in predisposition to CAD. Z. Chen and G. Ma contributed equally to this paper.     

Further evidence for the contribution of the vascular endothelial growth factor gene in coronary artery disease susceptibility

Coronary artery disease (CAD) receives intensive attentions in the research of cardiovascular diseases, due to its high incidence and severe impact on the quality of life vascular endothelial growth factor (VEGF), a potent angiogenic and vascular permeability factor, has been strongly implicated in the pathogenesis of CAD. Genetic markers in different regions of the VEGF gene have a plausible role in modulating the risk of CAD. To identify the markers contributing to the genetic susceptibility to CAD, we examined the potential association between CAD and 10 single nucleotide polymorphisms (SNPs, rs699947, rs1570360, rs2010963, rs833068, rs3024997, rs3025000, rs3025010, rs3025020, rs3025030, rs3025039) of the VEGF gene using the MassARRAY system. Participants included 242 CAD patients and 253 healthy controls from a Chinese Han Population (He'nan Province, China). The allelic or genotypic frequencies of the rs699947 (5′ untranslated regions, 5′UTR) and rs2010963 (5′UTR) polymorphisms in the CAD patients were significantly different from those in the healthy controls. The CAD patients had significantly higher frequency of the rs699947 A allele (χ² = 11.141, P = 0.001, OR = 1.665, 95% CI = 1.232–2.250) and rs2010963 C allele (χ² = 13.593, P = 0.0002, OR = 1.611, 95% CI = 1.249–2.077). Strong linkage disequilibrium was observed in the rs699947–rs1570360–rs2010963 haplotype block (D’ > 0.9). Significantly more C–G–C haplotypes (P = 0.040) and significantly fewer C–G–G haplotypes (P = 0.0004) were found in the CAD patients. The possible association of rs699947 and rs2010963 with CAD risks warrant confirmation in independent case–control studies and may be informative for future investigations on the pathogenesis of CAD.     

Association of GNB3 gene C825T polymorphism with coronary heart disease

The C825T polymorphism in the gene encoding the G protein beta 3 subunit (GNB3) causes enhanced G protein activation and the increased in vitro cell proliferation. We investigated the association of gene GNB3 C825T polymorphism with coronary artery disease (CAD) in the Russian population. A total of 313 patients with CAD diagnosed on the basis of clinical studies and coronary angyography were examined. The control group included 132 individuals that lacked clinical CAD symptoms and had matching profile of coronary artery disease risk factors. Blood pressure was measured using standard protocols. Increased levels of diastolic and systolic pressure was observed in both groups. The allele and genotype frequencies of this polimorphic marker were significantly higher in the CAD patients than in control. We found that the frequency of allele C and genotype CC was significantly higher in the CAD patients (OR = 1.55; P = 0.0079; OR = 1.63; P = 0.0215, respectively), which suggests higher risk of this pathology in carriers of allele C and genotype CC. Thus, in the Russian population coronary artery disease is associated with GNB3 allele C and genotype CC.     

Testing allele homogeneity: the problem of nested hypotheses

Background

Coronary artery disease (CAD), and one of its intermediate risk factors, dyslipidemia, possess a demonstrable genetic component, although the genetic architecture is incompletely defined. We previously reported a linkage peak on chromosome 5q31-33 for early-onset CAD where the strength of evidence for linkage was increased in families with higher mean low density lipoprotein-cholesterol (LDL-C). Therefore, we sought to fine-map the peak using association mapping of LDL-C as an intermediate disease-related trait to further define the etiology of this linkage peak. The study populations consisted of 1908 individuals from the CATHGEN biorepository of patients undergoing cardiac catheterization; 254 families (N = 827 individuals) from the GENECARD familial study of early-onset CAD; and 162 aorta samples harvested from deceased donors. Linkage disequilibrium-tagged SNPs were selected with an average of one SNP per 20 kb for 126.6-160.2 MB (region of highest linkage) and less dense spacing (one SNP per 50 kb) for the flanking regions (117.7-126.6 and 160.2-167.5 MB) and genotyped on all samples using a custom Illumina array. Association analysis of each SNP with LDL-C was performed using multivariable linear regression (CATHGEN) and the quantitative trait transmission disequilibrium test (QTDT; GENECARD). SNPs associated with the intermediate quantitative trait, LDL-C, were then assessed for association with CAD (i.e., a qualitative phenotype) using linkage and association in the presence of linkage (APL; GENECARD) and logistic regression (CATHGEN and aortas).

Results

We identified four genes with SNPs that showed the strongest and most consistent associations with LDL-C and CAD: EBF1, PPP2R2B, SPOCK1, and PRELID2. The most significant results for association of SNPs with LDL-C were: EBF1, rs6865969, p = 0.01; PPP2R2B, rs2125443, p = 0.005; SPOCK1, rs17600115, p = 0.003; and PRELID2, rs10074645, p = 0.0002). The most significant results for CAD were EBF1, rs6865969, p = 0.007; PPP2R2B, rs7736604, p = 0.0003; SPOCK1, rs17170899, p = 0.004; and PRELID2, rs7713855, p = 0.003.

Conclusion

Using an intermediate disease-related quantitative trait of LDL-C we have identified four novel CAD genes, EBF1, PRELID2, SPOCK1, and PPP2R2B. These four genes should be further examined in future functional studies as candidate susceptibility loci for cardiovascular disease mediated through LDL-cholesterol pathways.     

Haplotype study of the CYP4A11 gene and coronary artery disease in Han and Uygur populations in China

Background

CYP4A11 converts arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), which has a crucial role in the modulation of cardiovascular homeostasis. We assessed the association between the human CYP4A11 gene and coronary artery disease (CAD) in Han and Uygur populations in China.

Methods and Results

In the Han population, 361 CAD patients and 315 controls were genotyped for four single-nucleotide polymorphisms (SNPs) of the human CYP4A11 gene (rs9332978, rs4660980, rs3890011, rs1126742). In the Uygur population, 331 CAD patients and 182 controls were genotyped for the same four SNPs. Data were assessed via haplotype-based case–control studies. For the Han population, the significance of the recessive model of SNP3 (GG vs. CC+GC) between CAD patients and control subjects was retained after adjustment for EH, DM and smoking (for men, 95% CI: 1.173–3.013, P = 0.009). The G-G-T haplotype in CAD was significantly higher than that in the control group (P = 0.037). In the Uygur population, neither the distribution of genotypes and alleles for the four SNPs nor the distribution of haplotypes constructed with the same three SNPs showed a significant difference between CAD and control subjects.

Conclusions

The GG genotype of rs3890011 and the G-G-T haplotype in the CYP4A11 gene could be a useful genetic marker of CAD in Han populations in China.     

Association of polymorphism in the thermolabile 5, 10-methylene tetrahydrofolate reductase gene and hyperhomocysteinemia with coronary artery disease

Objective To determine the incidence of methylene tetrahydrofolate reductase (MTHFR) gene 677C→T polymorphism and plasma homocysteine (Hcy) levels in a group of subjects who underwent coronary angiography, in an attempt to establish a correlation between these parameters and the severity of coronary artery disease (CAD) and to investigate the correlation between hyperhomocysteinemia (HHcy) and the presence of 677C→T polymorphism. Background Elevated plasma Hcy level is an independent risk factor for CAD. A common mutation (677C→T) in the gene coding for MTHFR has been reported to reduce the enzymatic activity and is associated with elevated levels of Hcy, especially in subjects with low folate intake. Methods The study group comprised of 84 patients with CAD and 100 age-and-sex matched controls who had no history or clinical evidence of CAD and/or MI. DNA was extracted from peripheral blood and genotypes were determined by polymerase chain reaction, restriction mapping with Hinf1, and gel electrophoresis. Conventional risk factors for CAD were prospectively documented. Results Allele and genotype frequencies in cases and control subjects were compatible with Hardy–Weinberg equilibrium. The frequencies of TT, CT, and CC genotypes among CAD patients were 4.8, 27.4, and 67.8% and in controls were 1.0, 19.0, and 80%. Hcy levels were higher in patients with triple-vessel disease compared to single and double vessel disease (P = 0.002). Multivariate analyses identified HHcy, diabetes mellitus, and hypertension as the independent predictors of CAD. Conclusions HHcy appears to have a graded effect on the risk of CAD as well as the severity and extent of coronary atherosclerosis. Our findings support that homozygous genotype of MTHFR is a genetic risk factor for CAD. A further study with larger sample size including assessment of vitamin status is needed to better clarify the relationship between MTHFR genotypes and CAD.     

VKORC1 rs2359612C allele is associated with increased risk of coronary artery disease in the presence of coronary calcification

VKORC1 genetic polymorphisms affect warfarin dose response, aortic calcification, and the susceptibility of coronary artery disease as shown in our previous study. Little is known regarding the association of VKORC1 polymorphisms with coronary artery calcification (CAC) and the role of CAC in the association with coronary artery disease (CAD). Due to a natural haplotype block in the VKORC1 gene in Chinese, polymorphism rs2359612 was analyzed in a case–control study and a prospective study. The case–control study included 464 CAD patients with non-calcified plaque (NCP), 562 CAD patients with mixed calcified plaque (MCP), 492 subjects with calcified plaque (CP), and 521 controls. The rs2359612C was only associated with increased risk of MCP, the CAD in the presence of CAC; the odds ratio was 1.397 (95 % CI 1.008–1.937, P < 0.05), which was replicated in the second independent population. On the contrary, a negative correlation was observed between rs2359612 and log-transformed Agatston score, and rs2359612 was negatively associated with the number of calcified vessels. Moreover, in a prospective study including 849 CAD patients undergoing revascularization, rs2359612C predicted a higher incidence of cardiovascular events in MCP subgroup; the relative risk was 1.435 (95 % CI 1.008–2.041, P = 0.045), which was not observed in the NCP subgroup. We conclude that the rs2359612C was associated with a higher risk of CAD in the presence of CAC and a higher incidence of cardiovascular events in CAD patients with CAC, but a lower coronary calcification. VKORC1 polymorphisms may be associated with the endophenotype of CAD, calcification-related atherosclerosis.     

Association of the <Emphasis Type="Italic">rs1870634</Emphasis> Variant in Long Intergenic Non-protein Coding RNA 841 with Coronary Artery Disease: A GWAS-Replication Study in an Iranian Population

Recent genome-wide association studies (GWAS) identified a list of single-nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD). Replication of GWAS findings in different population corroborated the observed association in the parent GWAS. In this study, we aimed to replicate the association of rs1870634, a GWAS identified SNP, to CAD in an Iranian population. The study population consisted of 267 subjects undergoing coronary angiography coronary angiography including 155 CAD patients and 112 non-CAD age- and gender-matched controls. The genotype determination of rs1870634 SNP performed using high-resolution melting analysis (HRM) technique. Our results revealed that the GG genotype frequency was significantly higher in CAD patients compared with controls (P?=?0.03). The results of binary logistic regression suggested that this genotype was significantly associated with CAD risk adjustment for age, BMI, sex, TC, and LDL-C lipid levels (OR of 2.78, 95% CI (1.10–7.01), P?=?0.03). Moreover, our results showed that the GG+TG genotypes were 2.52 times more likely to develop CAD (95% CI 1.05–6.03) than TT genotype carriers after adjusting for age, sex, and lipid profiles (P?=?0.037). These data showed that the GG genotype could be associated with increased risk of CAD in a sample of Iranian population.     

Frequencies of C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene at the early stage of human development

In most cases, the cause of embryo and fetus death remains unclear although the multifactorial reasons are suspected. The polymorphic C677T and A1298C variants of the MTHFR gene are associated with hyperhomocysteinemia, which is a risk factor of early pregnancy loss. The aim of this study is analysis of genotypes and haplotypes of C677T and A1298C polymorphic variants of MTHFR genes in the groups of spontaneous abortions with normal karyotype and newborns in the Tomsk population. Between these groups, no statistically significant differences were determined in the allele, genotype, and haplotype distributions of C677T and A1298C polymorphisms of the MTHFR gene. The haplotype frequencies of C677T and A1298C polymorphic variants of MTHFR gene in the Russian populations, which proved to be similar to those in most European populations, are presented for the first time.     

The Effects of Overdominance on Linkage in a Multilocus System

Computer simulations were performed with overdominant multiple alleles among tightly linked multiple loci under a multiplicative fitness model. The quantity X²/N(n — 1) was introduced as a new measure of linkage disequilibrium which, unlike previously available measures, can be applied to multiple allele models, where N is the sample size, and n is the number of alleles at the locus possessing fewest alleles. Simulations showed that (1) With multiple (three or four) alleles, the approach to stable disequilibrium is slower and the amount of disequilibrium established is weaker than in a two allele system. (2) The number of complementary chromosomes is a function of number of alleles and of population size. (3) As population size increases, the rate of the approach to stable disequilibrium is slower. (4) There is an optimum selection coefficient which minimizes the transient fixation probability of alleles when linkage is present. (5) The absence of linkage disequilibrium is in most cases not a practical method of testing the hypothesis of balancing selection of genetic polymorphisms because it depends strongly on population size in determining linkage disequilibria.     

Multi-allelic haplotype association identifies novel information different from single-SNP analysis: A new protective haplotype in the LRP8 gene is against familial and early-onset CAD and MI

Our previous studies identified a functional SNP, R952Q in the LRP8 gene, that was associated with increased platelet activation and familial and early-onset coronary artery disease (CAD) and myocardial infarction (MI) in American and Italian Caucasian populations. In this study, we analyzed four additional SNPs near R952Q (rs7546246, rs2297660, rs3737983, rs5177) to identify a specific LRP8 SNP haplotype that is associated with familial and early-onset CAD and MI. We employed a case–control association design involving 381 premature CAD and MI probands and 560 controls in GeneQuest, 441 individuals from 22 large pedigrees in GeneQuest II, and 248 MI patients with family history and 308 controls in an Italian cohort. Like R952Q, LRP8 SNPs rs7546246, rs2297660, rs3737983, and rs5177 were significantly associated with early-onset CAD/MI in both population-based and family-based association studies in GeneQuest. The results were replicated in the GeneQuest II family-based population and the Italian population. We then carried out a haplotype analysis for all five SNPs including R952Q. One common haplotype (TCCGC) was significantly associated with CAD (P = 4.0 × 10^− 11) and MI (P = 6.5 × 10^− 12) in GeneQuest with odds ratios of 0.53 and 0.42, respectively. The results were replicated in the Italian cohort (P = 0.004, OR = 0.71). The sib-TDT analysis also showed significant association between the TCCGC haplotype and CAD in GeneQuest II (P = 0.001). These results suggest that a common LRP8 haplotype TCCGC confers a significant protective effect on the development of familial, early-onset CAD and/or MI.     

Associations of Polymorphisms in MTHFR Gene with the Risk of Age-Related Cataract in Chinese Han Population: A Genotype-Phenotype Analysis

Homocysteine (Hcy) is a potential risk factor for age-related cataract (ARC). Methylenetetrahydrofolate reductase (MTHFR) is the key enzyme for Hcy metabolism, and variants of MTHFR may affect MTHFR enzyme activity. This study mainly evaluated the associations between variants in MTHFR gene, plasma MTHFR enzyme activity, total Hcy (tHcy) levels and ARC risk in Chinese population. Four single nucleotide polymorphisms (SNPs) in MTHFR gene were genotyped using the high-resolution melting (HRM) method in 502 ARC patients (mean age, 70.2 [SD, 9.0], 46.0% male) and 890 healthy controls (mean age, 67.1 [SD, 11.1], 47.6% male). The plasma MTHFR activity, folic acid (FA), vitamins B12 and B6 levels were detected by enzyme-linked immunosorbent assays (ELISA). The plasma tHcy levels were measured by an automated enzymatic assay. After the Bonferroni correction, the minor allele T of SNP rs1801133 showed a significant association with an increased risk of overall ARC (OR = 1.26, P = 0.003). Consistent association was also found between SNP rs1801133 and cortical ARC risk (OR = 1.44, P = 0.003). Haplotype analyses revealed an adverse effect of the haplotype "C-A-T-C" (alleles in order of SNPs rs3737967, rs1801131, rs1801133 and rs9651118) on ARC risk (OR = 1.55, P = 0.003). Moreover, in a joint analysis of SNPs rs9651118 and rs1801133, subjects with two unfavorable genotypes had a 1.76-fold increased risk of ARC compared with the reference group, and a statistically significant dose-response trend (P_trend = 0.001) was also observed. Further, in healthy controls and patients with cortical ARC, the allele T of SNP rs1801133 and the increasing number of unfavorable genotypes were significantly correlated with decreased MTHFR activity as well as increased tHcy levels. However, there was no significant association between FA, vitamins B12, B6 levels and MTHFR variants. Our data indicated that variants in MTHFR gene might individually and jointly influence susceptibility to ARC by affecting MTHFR enzyme activity and tHcy levels.     

Association of TLR and TREM-1 gene polymorphisms with risk of coronary artery disease in a Russian population

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.