Total Outflow of High-Density Lipoprotein-Cholesteryl Esters from Plasma Is Decreased in a Model of 3/4 Renal Mass Reduction.

(1) Background: Previous studies have enriched high-density lipoproteins (HDL) using cholesteryl esters in rabbits with a three-quarter reduction in functional renal mass, suggesting that the kidneys participate in the cholesterol homeostasis of these lipoproteins. However, the possible role of the kidneys in lipoprotein metabolism is still controversial. To understand the role of the kidneys in regulating the HDL lipid content, we determined the turnover of HDL-cholesteryl esters in rabbits with a three-quarter renal mass reduction. (2) Methods: HDL subclass characterization was conducted, and the kinetics of plasma HDL-cholesteryl esters, labeled with tritium, were studied in rabbits with a 75% reduction in functional renal mass (Ntx). (3) Results: The reduced renal mass triggered the enrichment of cholesterol, specifically cholesteryl esters, in HDL subclasses. The exchange of cholesteryl esters between HDL and apo B-containing lipoproteins (VLDL/LDL) was not significantly modified in Ntx rabbits. Moreover, the cholesteryl esters of HDL and VLDL/LDL fluxes from the plasmatic compartment tended to decrease, but they only reached statistical significance when both fluxes were added to the Nxt group. Accordingly, the fractional catabolic rate (FCR) of the HDL-cholesteryl esters was lower in Ntx rabbits, concomitantly with its accumulation in HDL subclasses, probably because of the reduced mass of renal cells requiring this lipid from lipoproteins.

DNA Methylation of the IL-17A Gene Promoter Is Associated with Subclinical Atherosclerosis and Coronary Artery Disease: The Genetics of Atherosclerotic Disease Mexican Study.

The interleukin-17 (IL-17) has a crucial role during inflammation and has been associated with cardiovascular diseases, but its role in epigenetics is still poorly understood. Therefore, the aim of this study was to evaluate the DNA methylation status of the IL-17A gene promoter to establish whether it may represent a risk factor for subclinical atherosclerosis (SA) or clinical coronary artery disease (CAD). We included 38 patients with premature CAD (pCAD), 48 individuals with SA, and 43 healthy controls. Methylation in the CpG region of the IL-17A gene promoter was assessed via methylation-specific polymerase chain reaction (MSP). Individuals with SA showed increased methylation levels compared to healthy controls and pCAD patients, with p < 0.001 for both. Logistic regression analysis showed that high methylation levels represent a significant risk for SA (OR = 5.68, 95% CI = 2.38-14.03, p < 0.001). Moreover, low methylation levels of the IL-17A gene promoter DNA represent a risk for symptomatic pCAD when compared with SA patients (OR = 0.16, 95% CI = 0.06-0.41, p < 0.001). Our data suggest that the increased DNA methylation of the IL-17A gene promoter is a risk factor for SA but may be a protection factor for progression from SA to symptomatic CAD.

Cardiac Laterality: Surgical Results of Right Atrial Isomerism.

Right atrial isomerism (RAI) is a complex entity with varying diagnostic and treatment outcomes due to its rarity. Treatment options range from palliative to corrective surgeries, resulting in heterogeneous outcomes. The aim of this study was to analyze the results obtained after cardiac surgery in patients with RAI. A retrospective study was conducted, including patients diagnosed with RAI who underwent cardiac surgery. Their follow-up was from 1 January 2010 to 31 March 2020. Demographic characteristics and perioperative conditions were described. Thirty-eight patients were included, the median age was 4 years (IQR 2-9.2) and 57.9% were men. The main diagnoses were atrioventricular canal (63.2%) and pulmonary stenosis (55.3%). The most common surgical procedures were modified Blalock-Taussig shunt (65.8%) and total cavopulmonary connection with an extracardiac conduit fenestrated without cardiopulmonary bypass (15.9%). We did not find any factors associated with negative outcomes in these patients. The overall survival was 86.8%, with a better outcome in those who did not require reintubation (log rank, p < 0.01). The survival of RAI was similar to other centers. Individuals with RAI should be evaluated rigorously to determine an adequate repair strategy, considering high morbidity and mortality.

Association between Genetic Variants of CELSR2-PSRC1-SORT1 and Cardiovascular Diseases: A Systematic Review and Meta-Analysis.

A cluster of three genes CELSR2, PSRC1, and SORT1 has been associated with cardiovascular diseases. Thus, the aim of this study was (i) to perform a systematic review and updated meta-analysis of the association of three polymorphisms (rs646776, rs599839, and rs464218) of this cluster with cardiovascular diseases, and (ii) to explore by PheWAS signals of the three SNPs in cardiovascular diseases and to evaluate the effect of rs599839 with tissue expression by in silico tools. Three electronic databases were searched to identify eligible studies. The meta-analysis showed that the rs599839 (allelic OR 1.19, 95% CI 1.13-1.26, dominant OR 1.22, 95% CI 1.06-1.39, recessive OR 1.23, 95% CI 1.15-1.32), rs646776 (allelic OR 1.46, 95% CI 1.17-1.82) polymorphisms showed an increased risk for cardiovascular diseases. PheWas analysis showed associations with coronary artery disease and total cholesterol. Our results suggest a possible involvement of the CELSR2-PSRC1-SORT1 cluster variants in the risk association of cardiovascular diseases, particularly coronary artery disease.

Epigenetic Evaluation of the TBX20 Gene and Environmental Risk Factors in Mexican Paediatric Patients with Congenital Septal Defects.

The TBX20 gene has a key role during cardiogenesis, and it has been related to epigenetic mechanisms in congenital heart disease (CHD). The purpose of this study was to assess the association between DNA methylation status and congenital septal defects. The DNA methylation of seven CpG sites in the TBX20 gene promoter was analyzed through pyrosequencing as a quantitative method in 48 patients with congenital septal defects and 104 individuals with patent ductus arteriosus (PDA). The average methylation was higher in patients than in PDA (p < 0.001). High methylation levels were associated with a higher risk of congenital septal defects (OR = 4.59, 95% CI = 1.57-13.44, p = 0.005). The ROC curve analysis indicated that methylation of the TBX20 gene could be considered a risk marker for congenital septal defects (AUC = 0.682; 95% CI = 0.58-0.77; p < 0.001). The analysis of environmental risk factors in patients with septal defects and PDA showed an association between the consumption of vitamins (OR = 0.10; 95% CI = 0.01-0.98; p = 0.048) and maternal infections (OR = 3.10; 95% CI = 1.26-7.60; p = 0.013). These results suggest that differences in DNA methylation of the TBX20 gene can be associated with septal defects.

Increased Carotid Intima-Media Thickness in Asymptomatic Individuals Is Associated with the PCSK9 (rs2149041) Gene Polymorphism in the Mexican Mestizo Population: Results of the GEA Cohort.

The increase in carotid intima-media thickness (CIMT) and coronary artery calcification (CAC) are features of subclinical atherosclerosis that might be determined by the genetic background of patients. Among the multiple risk factors, the proprotein convertase subtilisin kexin type 9 (PCSK9) has a great impact on atheroma development. Then, we focused on the potential association of the PCSK9 gene polymorphism (rs2149041) with the risk of an increased CIMT. We included 881 unrelated, asymptomatic individuals (732 normal CIMT and 149 increased CIMT) who lacked coronary calcification (CAC score = 0). Under the recessive inheritance model and adjusted by several cardiovascular risk factors, the rs2149041 polymorphism, determined by TaqMan genotyping assay, was associated with a high risk of increased CIMT (OR = 2.10, 95% IC = 1.26-3.47, P recessive = 0.004). Our results suggest that the rs2149041 polymorphism could be a risk marker for increased CIMT in asymptomatic individuals without coronary artery disease determined by the absence of a CAC score.

Helicobacter pylori infection and DNMT3a polymorphism are associated with the presence of premature coronary artery disease and subclinical atherosclerosis. Data from the GEA Mexican Study.

BACKGROUND: The association between H. pylori infection and coronary artery disease (CAD) is well-known. Alterations in DNA methylation in CAD have been reported, which can be induced by H. pylori through the DNA demethylases (DNMTs). The objective was to analyze the association and interaction of H. pylori infection and DMNT3a gene polymorphisms with premature CAD (pCAD) and subclinical atherosclerosis (SA). METHODS: The study included 561 patients with pCAD, 318 subjects with SA, and 599 healthy controls. Antibodies against H. pylori and DNMT3a rs13420827, rs752208, and rs1550117 polymorphisms were determined. RESULTS: The pCAD group presented the highest seroprevalence of H. pylori infection (87.7%) compared to the SA (74.5%, p = 1 × 10-6) and the control group (63.1%, p = 7 × 10-23). A significant association was observed between H. pylori infection and pCAD (OR = 2.729, p = 1.0 × 10-6). The rs13420827 polymorphism was associated with a high risk of H. pylori infection in the whole population (padditive = 0.009, pdominant = 0.018, and pcodominant2 = 0.013) and in individuals with SA (padditive = 0.003, pdominant = 0.020, precessive = 0.013, and pcodominant2 = 0.005). The coexistence of H. pylori infection and the rs13420827GG genotype increases the risk of pCAD (pinteraction = 1.1 × 10-5). CONCLUSIONS: According to the model adjusted for more confounding variables, H. pylori infection was associated with almost three times the risk of developing pCAD. The rs13420827G allele was associated with an increased risk of H. pylori infection in the whole population and in individuals with SA. Individuals in whom H. pylori infection and the rs13420827GG genotype coexist are at increased risk of pCAD.

Osteoprotegerin Gene Polymorphisms Are Associated with Subclinical Atherosclerosis in the Mexican Mestizo Population.

Subclinical atherosclerosis (SA) is the presence of coronary calcification in the absence of cardiovascular symptoms, and it usually progresses to atherosclerotic disease. Studies have shown an association of osteoprotegerin gene (OPG) variants with calcification process in cardiovascular diseases; however, to this day there are no studies that evaluate individuals in the asymptomatic stage of atherosclerotic disease. Therefore, the purpose of this study was to analyze the association of four genetic variants and haplotypes of the OPG gene with the development of SA, through TaqMan genotyping assays. We also aimed to identify potential response elements for transcription factors in these genetic variants. The study included 1413 asymptomatic participants (1041 were controls and 372 were individuals with SA). The rs3102735 polymorphism appeared as a protective marker (OR = 0.693; 95% CI = 0.493−0.974; pheterozygote = 0.035; OR = 0.699; 95% CI = 0.496−0.985; pcodominant 1 = 0.040) and two haplotypes were associated with SA, one as a decreased risk: GACC (OR = 0.641, 95% CI = 0.414−0.990, p = 0.045) and another as an increased risk: GACT (OR = 1.208, 95% CI = 1.020−1.431, p = 0.029). Our data suggest a lower risk of SA in rs3102735 C carriers in a representative sample of Mexican mestizo population.

DNA Methylation Levels of the TBX5 Gene Promoter Are Associated with Congenital Septal Defects in Mexican Paediatric Patients.

The TBX5 gene regulates morphological changes during heart development, and it has been associated with epigenetic abnormalities observed in congenital heart defects (CHD). The aim of this research was to evaluate the association between DNA methylation levels of the TBX5 gene promoter and congenital septal defects. DNA methylation levels of six CpG sites in the TBX5 gene promoter were evaluated using pyrosequencing analysis in 35 patients with congenital septal defects and 48 controls. Average methylation levels were higher in individuals with congenital septal defects than in the controls (p < 0.004). In five CpG sites, we also found higher methylation levels in patients than in the controls (p < 0.05). High methylation levels were associated with congenital septal defects (OR = 3.91; 95% CI = 1.02-14.8; p = 0.045). The analysis of Receiver Operating Characteristic (ROC) showed that the methylation levels of the TBX5 gene could be used as a risk marker for congenital septal defects (AUC = 0.68, 95% CI = 0.56-0.80; p = 0.004). Finally, an analysis of environmental factors indicated that maternal infections increased the risk (OR = 2.90; 95% CI = 1.01-8.33; p = 0.048) of congenital septal defects. Our data suggest that a high DNA methylation of the TBX5 gene could be associated with congenital septal defects.

Osteopontin Gene Polymorphisms Are Associated with Cardiovascular Risk Factors in Patients with Premature Coronary Artery Disease.

Osteopontin (OPN) is considered a clinical predictor of cardiovascular disease. We aimed to evaluate the association of the OPN gene polymorphisms rs2728127 and rs11730582 with the development of premature coronary artery disease (pCAD), cardiovascular risk factors, and cardiometabolic parameters. We evaluated 1142 patients with pCAD and 1073 controls. Both polymorphisms were determined by Taqman assays. Similar allele and genotype frequencies were observed in both groups; additionally, an association of these polymorphisms with CAD and cardiometabolic parameters was observed in both groups. In patients with pCAD, the rs11730582 was associated with a high risk of hypoadiponectinemia (OR = 1.300, P additive = 0.003), low risk of hypertension (OR = 0.709, P codominant 1 = 0.030), and low risk of having high non-HDL cholesterol (OR = 0.637, P additive = 0.038). In the control group, the rs2728127 was associated with a low risk of fatty liver (OR = 0.766, P additive = 0.038); while the rs11730582 was associated with a low risk of hypoadiponectinemia (OR = 0.728, P dominant = 0.022), and risk of having elevated apolipoprotein B (OR = 1.400, P dominant = 0.031). Our results suggest that in Mexican individuals, the rs11730582 and rs2728127 OPN gene polymorphisms are associated with some abnormal metabolic variables in patients with pCAD and controls.

The role of TaqI, ApaI and BsmI polymorphisms of VDR gene in lumbar spine pathologies: systematic review and meta-analysis.

PURPOSE: The objective of the present meta-analysis was to evaluate the association between TaqI (rs731236), ApaI (rs7975232) and BsmI (rs1544410) polymorphisms of the VDR gene and lumbar spine pathologies such as lumbar disc herniation and lumbar disc degeneration. BACKGROUND: VDR gene polymorphisms have been reported to be associated with an increased risk of lumbar spine pathologies. MATERIALS AND METHODS: A systematic search was performed up to February 2020 using PubMed, EBSCO and Web of Science databases. We used the keywords and combinations "lumbar disc degeneration," "lumbar disc herniation," "lumbar spine pathologies" and "VDR polymorphism." Subsequently, we performed a meta-analysis with the results of the included studies. RESULTS: We found that the TaqI polymorphism was associated with an increased risk of developing lumbar spine pathologies (recessive model OR 1.25, 95% CI 1.01-1.54) and lumbar disc degeneration (allelic model OR 1.26, 95% CI 1.07-1.48; recessive model OR 1.34, 95% CI 1.06-1.69), but not with lumbar disc herniation. Additionally, ApaI was associated with an increased risk of developing lumbar spine pathologies (heterozygous model OR 1.45, 95% CI 1.06-1.98), but not with lumbar disc herniation or lumbar disc degeneration. CONCLUSIONS: Our findings indicate that TaqI and ApaI polymorphisms of the VDR gene are important risk factors for developing lumbar spine pathologies. Moreover, the TaqI polymorphism is a risk factor for lumbar disc degeneration.

Variants of PCSK9 Gene Are Associated with Subclinical Atherosclerosis and Cardiometabolic Parameters in Mexicans. The GEA Project.

BACKGROUND: Coronary artery disease (CAD) is a chronic, inflammatory, and complex disease associated with vascular risk factors. Nowadays, the coronary artery calcium (CAC) is a specific marker of the presence and extent of atherosclerosis. Additionally, CAC is a predictor of future coronary events in asymptomatic individuals diagnosed with subclinical atherosclerosis (CAC > 0). In this study, our aim is to evaluate the participation of two polymorphisms of the PCSK9 gene as genetic markers for developing subclinical atherosclerosis and cardiometabolic risk factors in asymptomatic individuals. METHODS: We analyzed two PCSK9 polymorphisms (rs2479409 and rs615563) in 394 individuals with subclinical atherosclerosis and 1102 healthy controls using real time- polymerase chain reaction (PCR). RESULTS: Under various inheritance models adjusted for different confounding factors, the rs2479409 polymorphism was associated with an increased risk of developing subclinical atherosclerosis (OR = 1.53, P recessive = 0.041). Both polymorphisms were significantly associated with several cardiometabolic parameters. CONCLUSIONS: Our data suggest that rs2479409 polymorphism could be envisaged as a risk marker for subclinical atherosclerosis.

Are functional variants of the microRNA-146a gene associated with primary knee OA? Evidence in Mexican mestizo population.

MicroRNA-146a (miR-146a) is an inflammatory response regulator whose expression is deregulated in osteoarthritis (OA); variations in the miR-146a gene could affect OA risk. This study aimed to analyze the association between two functional variants of the miR-146a gene and primary knee OA in Mexican mestizo population. Methods and Results. A case-control study was conducted with cases defined as individuals aged ≥ 40 years with primary knee OA grade ≥ 2, according to the Kellgren-Lawrence system. Controls were volunteers with no primary knee OA with radiographic grade < 2. TaqMan allelic discrimination assays genotyped the rs2910164 and rs57095329. Allelic and genotypic frequencies, as well as the Hardy-Weinberg equilibrium (HWE), were calculated. The genetic association was tested under codominant, dominant, and recessive models. Non-conditional logistic regressions were carried out to estimate the association magnitude. We included 310 cases and 379 controls. Despite rs2910164 being in HWE, there was no association under codominant, dominant, and recessive models. In women with OA grade 2, the codominant model found a trend between the CC genotype and increased risk [OR (95% CI) 1.6 (0.7-3.5)]; the same trend was found in OA grade 4 in the codominant and recessive models [1.8 (0.6-5.4) and 2.0 (0.7-5.9)]. Conversely, in men with OA grade 4, the CC genotype tended to be associated with a lower risk in the codominant and recessive models [0.6 (0.1-6.0) and 0.5 (0.1-5.1)]. Conclusion. Our results show that miR-146a gene variants are not significantly associated with primary knee OA in Mexican mestizos.

Evaluation of leptin levels in serum as a biomarker for suicide behavior: systematic review and meta-analysis.

Objective: We conducted a meta-analysis of case-control studies to determine whether leptin levels in serum contribute to the pathogenesis of suicide behavior.Methods: PubMed, EBSCO and Science Direct databases were used to search for relevant articles published before January 2020. The systematic review included nine case-control studies that measured leptin levels. The standardized mean difference (d) and 95% confidence intervals were calculated in a fixed-effects model and a random-effects model when appropriate.Results: The results of our meta-analysis indicated that individuals with suicide behavior presented reduced levels of leptin (d: -1.80, 95% CI: -2.21 to -01.38 ng/ml, I2 = 0, p(Q) = 0.59). Sensitivity and publication bias analyses confirmed these results.Conclusions: The current meta-analysis suggests that leptin levels might be associated with an increased risk of suicide behavior. However, more studies including larger sample sizes are needed to reach conclusive result.

The role of gene polymorphisms, and analysis of peripheral and central levels of interleukins in suicidal behavior: A systematic review.

In terms of the physiological characteristics of suicidal behavior (SB) disorder, an increase inflammation response has been reported in these individuals. Therefore, the pro-inflammatory and anti-inflammatory activities of interleukins are adequate markers to research in order to understand the pathogenesis of SB. For that reason, the aim of this systematic review was to evaluate the role of interleukins in individuals with suicidal behavior disorder. A systematic search was performed in PubMed, Scopus and EBSCO databases up to July 2019. We used the words "interleukin" AND "suicide", "interleukin" AND "suicidal", and "IL-". Articles where interleukins concentrations were measured in individuals with SB and/or genetic studies addressing interleukins genes variants as possible markers to SB were included. A total of 54 articles were included. Articles that measured interleukin levels comprised 1111 cases and 1588 controls; whereas the genetic studies comprised 3082 cases and 5148 controls. These studies evaluated the concentrations of IL-1ß, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, sIL-2R in serum, plasma. The pro-inflammatory interleukins concentrations were higher in cases than in controls; however, we observed heterogeneity in the measurements and sample sources. Whereas, 9 polymorphisms of IL-1α, IL-1ß, IL-6, IL-1ß-8 genes were analyzed in association with suicide behavior disorder, though no conclusive outcomes were attained. Our results suggest that individuals with suicide risk undergo continuous stress that could trigger the release and circulation of pro-inflammatory interleukins and therefore their concentration in plasma. However, more studies are necessary in order to reach conclusively outcomes.

Association between polymorphisms of FKBP5 gene and suicide attempt in a Mexican population: A case-control study.

Five polymorphisms (rs4713916, rs4713902, rs1360780, rs9296158 and rs3800373) of FKBP5 gene were analyzed in a case-control study comprising 423 Mexican individuals (146 individuals with suicide attempt and 277 controls). The SNP's were genotyped using the TaqMan-allelic assay. Genotype and allele frequencies were compared between the two groups, then the association between FKBP5 gene polymorphisms and suicide attempt was analyzed. We found a significant association of rs1360780 T minor allele (All, OR = 1.80, 95 % CI = 1.35-2.41, P = 0.0005; Males, OR = 2.25, 95 % CI = 1.44-3.50, P = 0.0002) as a suicide behavior risk factor. Conversely, rs3800373 C minor allele (All, OR = 0.61, 95 % CI = 0.46-0.83; P = 0.0013; Females, OR = 0.33, 95 % CI = 0.22-0.50; P = 0.0001) and the A-C-T-A-C haplotype (OR = 0.06, 95 % CI = 0.01-0.36; P = 0.002) were significantly associated as protective factors. No association was observed with the other SNP's. Our study suggests that SNP's in FKBP5 gene contribute to suicide behavior pathogenesis.

Association between congenital heart disease and NKX2.5 gene polymorphisms: systematic review and meta-analysis.

Aim: To analyze the association of NKX2.5 gene with congenital heart disease (CHD), and to determine if the variants rs703752, rs3729753 and rs2277923 increase the risk for developing CHD. Materials & methods: PubMed, EBSCO and Web of Science databases were screened to identify eligible studies. Through a comprehensive meta-analysis software, the association between NKX2.5 gene variants and susceptibility of CHD was calculated by pooled odd ratio (ORs) and 95% CI. Results: We observed that the allelic model of rs703752 and rs2277923 increased the risk in the overall population: OR = 1.24; 95% CI: 1.00-1.55; Z p-value = 0.049; OR = 1.18; 95% CI: 0.01-1.37; Z p-value = 0.036; respectively. Conclusion: Our results suggested that the rs703752 and rs2277923 polymorphisms of the NKX2.5 gene are associated with CHD.

The role of peripheral cortisol levels in suicide behavior: A systematic review and meta-analysis of 30 studies.

Cortisol can be considered as one biomarker for diagnosis of suicide; nevertheless, several studies have shown conflicting results. This study aimed to evaluate the levels of cortisol in individuals with suicide behavior and controls (healthy or with other psychiatric disorders). Published articles were searched on online databases (PubMed, Scopus and EBSCO). Standardized mean differences (SMD), heterogeneity, publication bias and sensitivity were assessed using the Comprehensive Meta-Analysis (CMA) statistical software. The meta-analysis comprised 30 studies that provided 1775 cases, and 2162 controls (696 healthy individuals and 1465 individuals with other psychiatric diagnoses). The pooled results revealed that cortisol levels were higher in individuals with suicide behavior (SMD = 0.92, 95%CI = 0.26; 1.57, P = 0.006; I2 = 88%, Q < 0.001) than healthy controls. However, individuals with suicide behavior showed decreased levels of cortisol in the morning. Additionally, individuals with suicide behavior showed lower levels of cortisol than psychiatric controls (SMD = -1.79, 95%CI = -3.01; -0.58, P = 0.004, I2 = 89%, Q < 0.001). Morning cortisol levels in individuals with suicide behavior were higher than morning cortisol levels in psychiatric controls. Our updated meta-analysis suggests that peripheral levels of cortisol have a role in suicide behavior.

Genetic Variants and Haplotypes in OPG Gene Are Associated with Premature Coronary Artery Disease and Traditional Cardiovascular Risk Factors in Mexican Population: The GEA Study.

Basic and clinical research have demonstrated that osteoprotegerin (OPG) plays an important role in the development and progression of cardiovascular diseases. The aim of this study was to evaluate the association of four polymorphic sites (rs2073618, rs3134069, rs3134070, and rs3102735) of OPG gene with premature coronary artery disease (pCAD), and with cardiometabolic parameters. The polymorphisms were genotyped using 5' exonuclease TaqMan genotyping assays with real-time PCR in 1098 individuals with pCAD and 1041 healthy controls. rs2073618 polymorphism was associated with a high risk of developing pCAD according to different inheritance models: additive (p = 0.001; odds ratio [OR] = 1.283), dominant (p = 0.006; OR = 1.383), recessive (p = 0.011; OR = 1.423), and codominant 2 (p = 0.001; OR = 1.646). The four polymorphisms were associated with different cardiovascular risk factors in individuals with pCAD and controls. Our results suggest that OPG rs2073618 polymorphism is associated with an increased risk of pCAD. In addition, two haplotypes were associated with pCAD, one increasing the risk (CACT) and another one as protective (GACC).