A Potential Association between Abdominal Obesity and the Efficacy of Humoral Immunity Induced by COVID-19 and by the AZD1222, Convidecia, BNT162b2, Sputnik V, and CoronaVac Vaccines.

Abdominal obesity is highly prevalent in Mexico and has a poor prognosis in terms of the severity of coronavirus disease (COVID-19) and low levels of antibodies induced by infection and vaccination. We evaluated the humoral immune response induced by COVID-19 and five different vaccination schedules in Mexican individuals with abdominal obesity and the effects of other variables. This prospective longitudinal cohort study included 2084 samples from 389 participants. The levels of anti-S1/S2 and anti-RBD IgG antibodies were measured at various time points after vaccination. A high prevalence of hospitalization and oxygen use was observed in individuals with abdominal obesity (AO) who had COVID-19 before vaccination; however, they also had high levels of anti-S1/S2 and anti-RBD-neutralizing IgG antibodies. The same was true for vaccination-induced antibody levels. However, their longevity was low. Interestingly, we did not observe significant differences in vaccine reactogenicity between abdominally obese and abdominally non-obese groups. Finally, individuals with a higher body mass index, older age, and previous COVID-19 had higher levels of antibodies induced by COVID-19 and vaccination. Therefore, it is important to evaluate other immunological and inflammatory factors to better understand the pathogenesis of COVID-19 in the presence of risk factors and to propose effective vaccination schedules for vulnerable populations.

Association of Obesity with SARS-CoV-2 and Its Relationship with the Humoral Response Prior to Vaccination in the State of Mexico: A Cross-Sectional Study.

Obesity is associated with an increased risk of contracting infections. This study aimed to estimate the risk of COVID-19 infection associated with obesity and to assess its role in the specific antibody response against SARS-CoV-2 in 2021. This study included 980 participants from the State of Mexico who participated in a serological survey where they were tested for SARS-CoV-2 IgG anti-S1/S2 and anti-RBD antibodies and asked for height, weight, and previous infection data via a questionnaire. Of the cohort of 980 participants, 451 (46.02%) were seropositive at the time of recruitment (45.2% symptomatic and 54.8% asymptomatic). The risk of SARS-CoV-2 infection with obesity was 2.18 (95% CI: 1.51-3.16), 2.58 (95% CI: 1.63-4.09), and 1.88 (95% CI: 1.18-2.98) for seropositive, asymptomatic, and symptomatic individuals, respectively, compared to those with normal weight. Anti-S1/S2 and anti-RBD IgG antibodies tended to be higher in overweight and obese participants in the seropositive group and stratified by different obesity classes. Additionally, there was a positive correlation between anti-S1/S2 and anti-RBD IgG antibodies and BMI in both men and women in the seropositive group. Obesity is an independent risk factor for SARS-CoV-2 infection when adjusted for confounding variables; however, the relationship between BMI and anti-S1/S2 and anti-RBD IgG antibody levels differed markedly in the presence or absence of symptoms.

Association of the EPAS1 rs7557402 Polymorphism with Hemodynamically Significant Patent Ductus Arteriosus Closure Failure in Premature Newborns under Pharmacological Treatment with Ibuprofen.

Patent ductus arteriosus (PDA) is frequent in preterm newborns, and its incidence is inversely associated with the degree of prematurity. The first choice of pharmacological treatment is ibuprofen. Several genes, including EPAS1, have been proposed as probable markers associated with a genetic predisposition for the development of PDA in preterm infants. EPAS 1 NG_016000.1:g.84131C>G or rs7557402 has been reported to be probably benign and associated with familial erythrocytosis by the Illumina Clinical Services Laboratory. Other variants of EPAS1 have been previously reported to be benign for familial erythrocytosis because they decrease gene function and are positive for familial erythrocytosis because the overexpression of EPAS1 is a key factor in uncontrolled erythrocyte proliferation. However, this could be inconvenient for ductal closure, since for this process to occur, cell proliferation, migration, and differentiation should take place, and a decrease in EPAS1 gene activity would negatively affect these processes. Single-nucleotide polymorphisms (SNPs) in EPAS1 and TFAP2B genes were searched with high-resolution melting and Sanger sequencing in blood samples of preterm infants with hemodynamically significant PDA treated with ibuprofen at the National Institute of Perinatology. The variant rs7557402, present in the EPAS1 gene eighth intron, was associated with a decreased response to treatment (p = 0.007, OR = 3.53). The SNP rs7557402 was associated with an increased risk of pharmacological treatment failure. A probable mechanism involved could be the decreased activity of the product of the EPAS1 gene.

Genetic polymorphisms rs1800871 and rs1800872 of IL-10 gene are associated with dengue infection, especially with serotype 1 and DwoWS in Mexican population.

INTRODUCTION: Dengue infection is generated by a complex interaction between DENV (Dengue Virus) and the host's immune response. Interleukin-10 is an immunoregulatory cytokine during DENV infection. The objective of this study was to investigate whether genetic variants in IL-10 could be useful as a predictive and susceptibility marker in the prognosis of DENV infection, particularly with serotype 1, and in participants with dengue without warning signs. MATERIAL AND METHODS: A study of cases (n = 365) and controls (n = 364) was carried out. Genotyping was performed by real-time PCR using TaqMan probes. Sample size power was calculated using Quanto software RESULTS: This is the first report showing the independent association of the T allele of rs1800871 (P = 0.023) and the A allele of rs1800872 (P = 0.010) with the risk of dengue infection. Statistical analysis established the genotypic association of IL-10 SNPs with DENV infection under different inheritance models. Our results also showed the association of the CC, TC, and CA haplotypes (P = 0.0064, P = 0.0032, and P = 0.0010 respectively) with infection. Furthermore, both polymorphic sites were associated with the risk of DwoWS and serotype 1 (Den-1) under different inheritance models. Finally, under the dominant model, we identified a positive correlation between IL-10 levels vs. IFN-γ and IL-8. CONCLUSION: Our results show the first independent association of the T and A alleles of the polymorphic sites rs1800871 and rs1800872, with dengue infection, particularly with Den-1, and in participants with DwoWs.

Longevity and Neutralizing Capacity of IgG Antibodies against SARS-CoV-2 Generated by the Application of BNT162b2, AZD1222, Convidecia, Sputnik V, and CoronaVac Vaccines: a Cohort Study in the Mexican Population.

The WHO has approved the use of several vaccines during the COVID-19 pandemic; experience over the last 2 years has indicated that dose demand can only be covered using more than one design. Therefore, having scientific evidence of the performance of the different vaccines applied in a country is highly relevant. In Mexico, 5 vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were used, allowing a cohort study to analyze the generation of anti-S1/S2 IgG antibodies and anti-RBD antibodies with neutralizing activity at 0, 21, 90, and 180 days after vaccination. Five groups of participants were formed on the basis of the type of vaccine received and were divided on the basis of whether they previously had or did not have COVID-19. After completing the vaccination schedule, the seroprevalence was 95.5, 97.5, 81.0, 95.2, and 90.0% (BNT162b2, AZD1222, Convidecia, Sputnik V, and CoronaVac, respectively). Among the participants without COVID-19 prior to vaccination, the largest amount of antibodies in the 90-day period was observed in the BNT162b2 group, and the amount of antibodies in the Sputnik V group decreased the least over time. Even though the percentages of seroconversion obtained in this study were lower than those currently reported in other parts of the world, the tested vaccines are able, in most cases, to induce a good production of IgG antibodies anti-S1/S2 and neutralizing capacity. The fact that there are people who have not produced antibodies during the study leaves open some questions that must be investigated to avoid the appearance of serious cases of COVID-19. IMPORTANCE Since the start of the vaccination programs against COVID-19 in 2020, it was evident that due to global shortages, the demand for the dose required in Mexico could only be covered by acquiring different vaccines. Therefore, determining the effectiveness of these and the longevity of acquired immunity is extremely important in a scenario where SARS-CoV-2 circulation becomes endemic and booster doses are required periodically. Our data reveal significant differences both in the generation of antibodies as well as in their longevity for the vaccines applied in the country but suggest that, in general, the Mexican population can reach a high capacity to neutralize the virus, therefore, regarding less the variant for which they were designed.

Common Variants in IL-20 Gene are Associated with Subclinical Atherosclerosis, Cardiovascular Risk Factors and IL-20 Levels in the Cohort of the Genetics of Atherosclerotic Disease (GEA) Mexican Study.

Inflammation has been involved in the development of atherosclerosis, type 2 diabetes mellitus, insulin resistance, and obesity. Interleukin 20 is a pro-inflammatory cytokine encoded by a polymorphic gene located in chromosome 1. The aim of the study was to evaluate the association of two IL-20 polymorphisms (rs1400986 and rs1518108) with subclinical atherosclerosis (SA), cardiovascular risk factors and IL-20 levels in a cohort of Mexican individuals. The polymorphisms were determined in 274 individuals with SA and 672 controls. Under different models, rs1400986 (OR = 0.51, Pcodominant1 = 0.0001; OR = 0.36, Pcodominant2 = 0.014; OR = 0.49, Pdominant = 0.0001 and OR = 0.55, Padditive = 0.0001) and rs1518108 (OR = 0.62, Pcodominant2 = 0.048 and OR = 0.79, Padditive = 0.048) were associated with a lower risk of SA. These polymorphisms were associated with cardiovascular risk factors in individuals with SA and controls. Controls with the rs1400986 TT genotype presented high levels of IL-20 (p = 0.031). In individuals with the rs1400986 CC genotype, we observed a negative correlation between IL-20 levels and total abdominal tissue (TAT), visceral abdominal tissue (VAT) and subcutaneous abdominal tissue (SAT). Our results indicate that the IL-20 rs1400986 and rs1518108 polymorphisms were associated with decreased risk of developing SA and with some cardiovascular risk factors in individuals with SA and healthy controls. Negative correlation between BMI and VAT/SAT ratio in individuals with rs1400986 CC genotype and among IL-20 levels and TAT, VAT and SAT was observed.

The IL-10-1082 (rs1800896) G allele is associated with a decreased risk of developing premature coronary artery disease and some IL-10 polymorphisms were associated with clinical and metabolic parameters. The GEA study.

Interleukin 10 (IL-10) is an anti-inflammatory cytokine with a protective role in the formation and the development of the atherosclerotic plaque. The aim of the present study was to establish if IL-10 gene polymorphisms are associated with the development of premature coronary artery disease (pCAD) and cardiovascular risk factors in Mexican individuals. Three IL-10 gene polymorphisms [-592C/A (rs1800872), -819C/T (rs1800871), and -1082 A/G (rs1800896)] and IL-10 plasma levels were analyzed in 2266 individuals (1160 pCAD patients and 1106 healthy controls). Under recessive and co-dominant2 models, the -1082 A/G (rs1800896) G allele was associated with decreased risk of developing pCAD (OR = 0.572, Prec = 0.022 and OR = 0.567, Pcod2 = 0.023). In pCAD patients, the polymorphisms were associated with hyperinsulinemia, small and dense LDLs, hypertension, and diabetes mellitus. In the control group, the polymorphisms were associated with hypertension, hyperuricemia, and small and dense LDLs. pCAD patients have significantly higher IL-10 plasma levels than healthy controls [0.91 (0.55-1.67) pg/mL vs 0.45 (0.24-0.98) pg/mL, respectively, P < 0.0001]. Nevertheless, these levels were not associated with the genotypes analyzed in the present study. The results suggest that the IL-10-1082 A/G (rs1800896) G allele is associated with a decreased risk of developing pCAD. In patients and controls, the polymorphisms analyzed were associated with some cardiovascular risk factors. Although, in pCAD patients the IL-10 plasma levels were higher, they were not associated with the genotypes of the polymorphisms examined.

IL-15 polymorphisms are associated with subclinical atherosclerosis and cardiovascular risk factors. The Genetics of Atherosclerosis Disease (GEA) Mexican Study.

Interleukin IL-15 (IL-15) has been implicated in the development of coronary artery disease (CAD). The aim of the present study was to evaluate the role of IL-15 gene polymorphisms as susceptibility markers for development of subclinical atherosclerosis (SA) and cardiovascular risk factors in Mexican population. Four IL-15 gene polymorphisms (rs4956403, rs3806798, rs1057972 and rs10833) were analyzed in a group of 397 individuals with SA and 1120 controls. Under different inheritance models adjusted by traditional risk factors, the rs10833T allele was associated with increased risk of developing SA [OR=1.42, Pcodom1=0.046; OR=1.48, Pdom=0.021; OR=1.43, Padd=0.014]. Under a dominant model, the rs1057972 polymorphism was associated with central obesity (P=0.045) and fatty liver (P=0.021), while the rs10833 polymorphism was associated with metabolic syndrome (P=0.007) in individuals with SA. The TAC haplotype was significantly associated with a decreased risk of SA. Individuals with rs10833CC genotype exhibited higher levels of IL-15 than individuals with CT+TT genotypes. The results suggest that IL-15 polymorphisms are involved in the risk of developing SA and are associated with metabolic syndrome, central obesity and fatty liver in our study population. The rs10833 polymorphism could be involved in regulating IL-15 production in SA.

The NLRP3 and CASP1 gene polymorphisms are associated with developing of acute coronary syndrome: a case-control study.

The protein products of NLRP3 and CASP1 genes are involved in the cleavage of pro-IL-1B and pro-IL-18 leading to the active cytokines, which play an important role in the development of the acute coronary syndrome (ACS). The aim of the present study was to evaluate whether NLRP3 and CASP1 gene polymorphisms are biomarkers of ACS susceptibility in Mexican population. Two polymorphisms of the CASP1 gene [G+7/in6A (rs501192) and A10370-G Exon-6 (rs580253)] and one of the NLRP3 gene [UTR'3 G37562-C (rs10754558)] were genotyped by 5' exonuclease TaqMan assays in a group of 617 patients with ACS and 609 control individuals. Under recessive model, the CASP1 G+7/in6A polymorphism was associated with an increased risk of developing ACS when compared to healthy controls (OR = 1.76, 95% CI 1.08-2.86, P Res  = 0.022). In the same way, under recessive model, the CASP1 A10370-G was associated with increased risk of ACS (OR = 1.75, 95% CI 1.07-2.85, P Res  = 0.025). Moreover, under co-dominant, dominant, over-dominant, and additive models, the NLRP3 UTR'3 G37562-C was associated with a decreased risk of ACS (OR = 0.45, 95%CI 0.22-0.92, P Co-dom  = 0.006; OR = 0.61, 95%CI 0.44-0.84, P Dom  = 0.002; OR = 0.67, 95%CI 0.48-0.94, P Over-dom  = 0.02; and OR = 0.65, 95%CI 0.50-0.94, P Add  = 0.02, respectively). In summary, this study demonstrates that the G+7/in6A and A10370-G polymorphisms of the CASP1 gene are associated with increased risk of developing ACS, whereas the UTR'3 G37562-C polymorphism of the NLRP3 gene is associated with a decreased risk of developing ACS in Mexican population.

Prevalence of non-influenza respiratory viruses in acute respiratory infection cases in Mexico.

BACKGROUND: Acute respiratory infections are the leading cause of morbidity and mortality worldwide. Although a viral aetiological agent is estimated to be involved in up to 80% of cases, the majority of these agents have never been specifically identified. Since 2009, diagnostic and surveillance efforts for influenza virus have been applied worldwide. However, insufficient epidemiological information is available for the many other respiratory viruses that can cause Acute respiratory infections. METHODS: This study evaluated the presence of 14 non-influenza respiratory viruses in 872 pharyngeal exudate samples using RT-qPCR. All samples met the operational definition of a probable case of an influenza-like illness or severe acute respiratory infection and had a previous negative result for influenza by RT-qPCR. RESULTS: The presence of at least one non-influenza virus was observed in 312 samples (35.8%). The most frequent viruses were rhinovirus (RV; 33.0%), human respiratory syncytial virus (HRSV; 30.8%) and human metapneumovirus (HMPV; 10.6%). A total of 56 cases of co-infection (17.9%) caused by 2, 3, or 4 viruses were identified. Approximately 62.5% of all positive cases were in children under 9 years of age. CONCLUSION: In this study, we identified 13 non-influenza respiratory viruses that could occur in any season of the year. This study provides evidence for the prevalence and seasonality of a wide range of respiratory viruses that circulate in Mexico and constitute a risk for the population. Additionally, our data suggest that including these tests more widely in the diagnostic algorithm for influenza may reduce the use of unnecessary antibiotics, reduce the hospitalisation time, and enrich national epidemiological data with respect to the infections caused by these viruses.

Interleukin 35 Polymorphisms Are Associated with Decreased Risk of Premature Coronary Artery Disease, Metabolic Parameters, and IL-35 Levels: The Genetics of Atherosclerotic Disease (GEA) Study.

Interleukin 35 (IL-35) is a heterodimeric cytokine involved in the development of atherosclerosis. The aim of the present study was to establish if the polymorphisms of IL-12A and EBI3 genes that encode the IL-35 subunits are associated with the development of premature coronary artery disease (CAD) in Mexican individuals. The IL-12A and EBI3 polymorphisms were determined in 1162 patients with premature CAD and 873 controls. Under different models, the EBI3 rs428253 (OR = 0.831, Padd = 0.036; OR = 0.614, Prec = 0.033; OR = 0.591, Pcod2 = 0.027) and IL-12A rs2243115 (OR = 0.674, Padd = 0.010; OR = 0.676, Pdom = 0.014; OR = 0.698, Phet = 0.027; OR = 0.694, Pcod1 = 0.024) polymorphisms were associated with decreased risk of developing premature CAD. Some polymorphisms were associated with clinical and metabolic parameters. Significant different levels of IL-35 were observed in EBI3 rs4740 and rs4905 genotypes only in the group of healthy controls. In summary, our study suggests that the EBI3 and IL-12A polymorphisms play an important role in decreasing the risk of developing premature CAD; it also demonstrates the relationship of the EBI3 rs4740 and rs4905 genotypes with IL-35 levels in healthy individuals.

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.

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.

PLA2G2A polymorphisms are associated with metabolic syndrome and type 2 diabetes mellitus. Results from the genetics of atherosclerotic disease Mexican study.

The secretory phospholipase A2 II A (sPLA2-IIA) encoded by PLA2G2A gene hydrolyzes phospholipids liberating free fatty acids (FFAs) and lysophospholipids. If lipolysis exceeds lipogenesis, the free fatty acids undergo a continuous release into circulation. A sustained excessive increase in this release contributes to metabolic disease. The aim of the present study was to evaluate the role of PLA2G2A gene polymorphisms as susceptibility markers for metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) in Mexican population. Three PLA2G2A gene polymorphisms (rs876018, rs3753827 and rs11573156) were genotyped by 5' exonuclease TaqMan assays in a group of 338 patients with T2DM, 460 individuals with MetS and 366 healthy controls. Under codominant 1(codom1), dominant (dom) and additive (add) models adjusted by age, gender, body mass index (BMI), smoking habit, and hypertension, the rs876018T allele was associated with increased risk of MetS [Odds Ratio (OR)=1.66, Pcodom1=0.005; OR=1.67, Pdom=0.003; OR=1.49, Padd=0.005] as compared to controls. On the other hand, under several models adjusted by the same variables, the rs3753827A (OR=1.52, Pcodom1=0.039 and OR=1.49, Pdom=0.039) and rs11573156C alleles (OR=6.46, Pcodom1=0.013; OR=6.70, Pcodom2=0.009; OR=6.65, Pdom=0.009) were associated with increased risk of T2DM when compared with controls. In addition, the rs876018T allele was associated with hypercholesterolemia (Pdom=0.017, Padd=0.009) and risk of subclinical atherosclerosis (SA) (Pdom=0.041) in MetS when compared with controls. Also, this allele was associated with SA in T2DM patients (Pdom=0.007). The TAG haplotype was significantly associated with increased risk of MetS (OR=1.54, P=0.006). Results suggest that PLA2G2A polymorphisms are involved in the risk of developing MetS and T2D and are associated with SA in this group of patients.

Receptor-interacting protein 2 (RIP2) gene polymorphisms are associated with increased risk of subclinical atherosclerosis and clinical and metabolic parameters. The Genetics of Atherosclerotic Disease (GEA) Mexican study.

The receptor-interacting protein 2 (Rip2) is a serine/threonine kinase involved in multiple nuclear factor-κB (NFκB) activation pathways and is a key regulator of cellular lipid metabolism and cardiovascular disease. The aim of the present study was to evaluate the role of RIP2 gene polymorphisms as susceptibility markers for subclinical atherosclerosis (SA). Using an informatics analysis, four RIP2 gene polymorphisms with predicted functional effects (rs2293808, rs43133, rs431264, and rs16900627) were selected. The polymorphisms were genotyped in 405 individuals with SA (calcium score>0 assessed by computed tomography) and 1099 controls (calcium score=0). Clinical, anthropometric, tomographic and biochemical traits were measured. The association between the RIP2 polymorphisms and SA was evaluated using logistic regression analyses. Pair wise linkage disequilibrium (LD, D') estimations between polymorphisms and haplotype reconstruction were performed with Haploview version 4:1. Under different models adjusted by age, gender, body mass index, hypertension, diabetes mellitus, smoking habit, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride levels, rs43133 (OR=1.43, 95% CI: 1.05-1.94, P=0.022), and rs16900627 (OR=1.59, 95% CI: 1.00-2.54, Pdom=0.048 and OR=1.60, 95% CI: 1.05-2.54, Padd=0.028) were associated with increased risk of developing SA. Moreover, rs2293808, and rs431264 were associated with clinical or metabolic parameters in SA individuals and in healthy controls. The four polymorphisms were in high linkage disequilibrium and the GAAG haplotype was associated with increased risk of developing SA (OR=1.47, P=0.027). This study shows for the first time, that RIP2 polymorphisms are associated with increased risk of SA and with some clinical and metabolic parameters.

In Silico Identification of Highly Conserved Epitopes of Influenza A H1N1, H2N2, H3N2, and H5N1 with Diagnostic and Vaccination Potential.

The unpredictable, evolutionary nature of the influenza A virus (IAV) is the primary problem when generating a vaccine and when designing diagnostic strategies; thus, it is necessary to determine the constant regions in viral proteins. In this study, we completed an in silico analysis of the reported epitopes of the 4 IAV proteins that are antigenically most significant (HA, NA, NP, and M2) in the 3 strains with the greatest world circulation in the last century (H1N1, H2N2, and H3N2) and in one of the main aviary subtypes responsible for zoonosis (H5N1). For this purpose, the HMMER program was used to align 3,016 epitopes reported in the Immune Epitope Database and Analysis Resource (IEDB) and distributed in 34,294 stored sequences in the Pfam database. Eighteen epitopes were identified: 8 in HA, 5 in NA, 3 in NP, and 2 in M2. These epitopes have remained constant since they were first identified (~91 years) and are present in strains that have circulated on 5 continents. These sites could be targets for vaccination design strategies based on epitopes and/or as markers in the implementation of diagnostic techniques.

Monocyte chemoattractant protein-1 gene (MCP-1) polymorphisms are associated with risk of premature coronary artery disease in Mexican patients from the Genetics of Atherosclerotic Disease (GEA) study.

The CC chemokine monocyte chemoattractant protein (MCP)-1/CCL2 is involved in the formation, progression, and destabilization of atheromatous plaques and plays an essential role in postinfarction remodeling. The aim of the present study was to evaluate the role of MCP-1 gene polymorphisms as susceptibility markers for premature coronary artery disease (CAD) and cardiovascular risk factors in the Mexican population. Four MCP-1 gene polymorphisms (rs1024611, rs2857654, rs3760396, and rs1024610) were genotyped by 5' exonuclease TaqMan assays in a group of 1072 patients with premature CAD, and 1082 healthy unrelated controls (with negative calcium score by computed tomography) seeking for associations with premature CAD and other metabolic and cardiovascular risk factors using logistic regression analyses. MCP-1 polymorphism frequencies were similar in premature CAD patients and healthy controls. When the analysis included only those premature CAD patients without type 2 diabetes mellitus (T2DM), the rs1024610 polymorphism was associated with increased risk of developing premature CAD under dominant and additive models adjusted by age and gender (OR=1.33, Pdom=0.040 and OR=1.34, Padd=0.027). The effect of the MCP-1 polymorphisms on various metabolic cardiovascular risk factors and metabolic parameters was explored separately in controls, and premature CAD. In this analysis adjusted by age and gender, the rs3760396 CC genotype was associated with low levels of gamma-glutamyl transpeptidase (P=0.002), whereas, the rs1024610 TT genotype was associated with decreased risk of T2DM (P=0.035) in premature CAD patients. One haplotype (CATG) was associated with increased risk of developing premature CAD (OR=1.44, P=0.0019). In summary, in our study, the rs1024610 polymorphism was associated with increased risk of developing premature CAD only in those patients without T2DM. The four MCP-1 polymorphisms were in high linkage disequilibrium and one haplotype was significantly associated with risk of developing premature CAD.

Novel mutations in the transcriptional activator domain of the human TBX20 in patients with atrial septal defect.

BACKGROUND: The relevance of TBX20 gene in heart development has been demonstrated in many animal models, but there are few works that try to elucidate the effect of TBX20 mutations in human congenital heart diseases. In these studies, all missense mutations associated with atrial septal defect (ASD) were found in the DNA-binding T-box domain, none in the transcriptional activator domain. METHODS: We search for TBX20 mutations in a group of patients with ASD or ventricular septal defect (VSD) using the High Resolution Melting (HRM) method and DNA sequencing. RESULTS: We report three missense mutations (Y309D, T370O, and M395R) within the transcriptional activator domain of human TBX20 that were associated with ASD. CONCLUSIONS: This is the first association of TBX20 transcriptional activator domain missense mutations with ASD. These findings could have implications for diagnosis, genetic screening, and patient follow-up.

Interleukin-17A gene haplotypes are associated with risk of premature coronary artery disease in Mexican patients from the Genetics of Atherosclerotic Disease (GEA) study.

AIM: The role of interleukin 17A (IL-17A) in the inflammatory process has caused interest in the potential significance of IL-17A as a biomarker for coronary artery disease (CAD). The aim of the present study was to evaluate the role of IL-17A gene polymorphisms as susceptibility markers for CAD in the Mexican population. METHODS: Four IL-17A gene polymorphisms (rs8193036, rs3819024, rs2275913 and rs8193037) were genotyped by 5' exonuclease TaqMan assays in a group of 900 patients with premature CAD and 667 healthy controls (with negative calcium score by computed tomography), seeking associations with CAD and other metabolic and cardiovascular risk factors using logistic regression analyses. RESULTS: No single IL-17A polymorphism was associated with premature CAD, however two haplotypes (CAGG and TAGA) were significantly associated with increased risk of premature CAD (OR = 1.35, 95% CI: 1.00-1.84, P = 0.018 and OR = 2.09, 95% CI: 1.16-3.76, P = 0.003, respectively). Moreover, rs3819024 was associated with increased levels of visceral abdominal fat (P = 0.002) and rs8193036 was significantly associated with risk of central obesity (P = 0.020), hypertriglyceridemia (P = 0.027), and metabolic syndrome (P = 0.027) in the premature CAD group, under dominant models adjusted by age, gender, BMI, smoking history, alcohol consumption, and treatment. CONCLUSION: The results suggest that IL-17A haplotypes are involved in the risk of developing premature CAD and some IL-17A polymorphisms are associated with cardiovascular risk factors in Mexican individuals with premature CAD.

Association of the C-type lectin-like domain family-16A (CLEC16A) gene polymorphisms with acute coronary syndrome in Mexican patients.

The CLEC16A gene has an important role in the immune activation and regulation inflammatory. This gene encodes to C-type lectin domain that is involved in the recognition of DAMPS. The aim of this study was assess the CLEC16A gene polymorphisms in the risk of developing ACS in a group of patients. Four rs12708716, rs12917716, rs6498142 and rs9925481 (positions 146529 A>G, 155804 G>C, 47905 C>G and 64135 C>T, respectively) single nucleotide polymorphisms of CLEC16A gene were analyzed by TaqMan assays in a group of 452 patients with ACS and 456 healthy controls. The analysis was performed on the total group of individuals and then in groups of men and women separately. Under co-dominant model adjusted by cardiovascular risk factors the rs12708716 (146529 A>G) and rs12917716 (155804 G>C) polymorphisms were significantly associated with decrease risk of ACS in men (OR=0.16, PCo-dom=0.027 and OR=0.37, PCo-dom=0.016, respectively). In summary, our data suggests that two polymorphisms of the CLEC16A gene play an important role in the developing of ACS in men.

The (G>A) rs11573191 polymorphism of PLA2G5 gene is associated with premature coronary artery disease in the Mexican Mestizo population: the genetics of atherosclerotic disease Mexican study.

Coronary artery disease (CAD) is a multifactorial disorder that results from an excessive inflammatory response. Secretory phospholipase A2-V (sPLA2-V) encoded by PLA2G5 gene promotes diverse proinflammatory processes. The aim of the present study was to analyze if PLA2G5 gene polymorphisms are associated with premature CAD. Three PLA2G5 polymorphisms (rs11573187, rs2148911, and rs11573191) were analyzed in 707 patients with premature CAD and 749 healthy controls. Haplotypes were constructed after linkage disequilibrium analysis. Under dominant, recessive, and additive models, the rs11573191 polymorphism was associated with increased risk of premature CAD (OR = 1.51, P(dom) = 3.5 × 10(-3); OR = 2.95, P(rec) = 0.023; OR = 1.51, P(add) = 1.2 × 10(-3)). According to the informatics software, this polymorphism had a functional effect modifying the affinity of the sequence by the MZF1 transcription factor. PLA2G5 polymorphisms were in linkage disequilibrium and the CGA haplotype was associated with increased risk of premature CAD (OR = 1.49, P = 0.0023) and with hypertension in these patients (OR = 1.75, P = 0.0072). Our results demonstrate the association of the PLA2G5 rs11573191 polymorphism with premature CAD. In our study, it was possible to distinguish one haplotype associated with increased risk of premature CAD and hypertension.