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.

Vitamin D Deficiency is not Associated with Fatty Liver in a Mexican Population.

INTRODUCTION AND AIM: Association of vitamin D deficiency (VDD) with fatty liver (FL) disease is controversial. The purpose of this study was to analyze the association of VDD with FL. MATERIAL AND METHODS: Cross-sectional study. Data on cardiovascular risk factors, medications, alcohol intake, smoking, diet, and physical activity were obtained. Biochemical, anthropometric, and blood pressure variables were measured. The 25-hydroxyvitamin D (25(OH)D) was quantified through chemoluminescence. The presence of FL, defined as a liver/spleen attenuation index lower than 1.0, was identified through computed axial tomography (CAT). RESULTS: The study included 1,467 subjects (49.7% men) with a mean age of 53.3 ± 9.3 years and BMI of 28.3 ± 4.0 kg/m2. Only 11% had optimum values of vitamin D, and 25(OH)D concentration was lower in participants with FL. Multivariate logistic regression models, adjusted for age, gender, BMI, sampling season, glucose, total cholesterol, triglycerides, HOMA-IR, hs-CRP, ALT, AST, and elevated VAT, revealed an association between FL and vitamin D (VD) insufficiency (RM 1.61 [0.99-2.61]) and with VDD (RM 1.68 [1.02-2.77]); however, statistical significance was lost when including caloric consumption and physical activity in the model. CONCLUSIONS: In Mexican adults, deficient VD concentration and FL were not independently associated of caloric consumption and physical activity.

Trypanosoma cruzi vaccine candidate antigens Tc24 and TSA-1 recall memory immune response associated with HLA-A and -B supertypes in Chagasic chronic patients from Mexico.

Trypanosoma cruzi antigens TSA-1 and Tc24 have shown promise as vaccine candidates in animal studies. We evaluated here the recall immune response these antigens induce in Chagasic patients, as a first step to test their immunogenicity in humans. We evaluated the in vitro cellular immune response after stimulation with recombinant TSA-1 (rTSA-1) or recombinant Tc24 (rTc24) in mononuclear cells of asymptomatic Chagasic chronic patients (n = 20) compared to healthy volunteers (n = 19) from Yucatan, Mexico. Proliferation assays, intracellular cytokine staining, cytometric bead arrays, and memory T cell immunophenotyping were performed by flow cytometry. Peripheral blood mononuclear cells (PBMC) from Chagasic patients showed significant proliferation after stimulation with rTc24 and presented a phenotype of T effector memory cells (CD45RA-CCR7-). These cells also produced IFN-γ and, to a lesser extent IL10, after stimulation with rTSA-1 and rTc24 proteins. Overall, both antigens recalled a broad immune response in some Chagasic patients, confirming that their immune system had been primed against these antigens during natural infection. Analysis of HLA-A and HLA-B allele diversity by PCR-sequencing indicated that HLA-A03 and HLA-B07 were the most frequent supertypes in this Mexican population. Also, there was a significant difference in the frequency of HLA-A01 and HLA-A02 supertypes between Chagasic patients and controls, while the other alleles were evenly distributed. Some aspects of the immune response, such as antigen-induced IFN-γ production by CD4+ and CD8+ T cells and CD8+ proliferation, showed significant association with specific HLA-A supertypes, depending on the antigen considered. In conclusion, our results confirm the ability of both TSA-1 and Tc24 recombinant proteins to recall an immune response induced by the native antigens during natural infection in at least some patients. Our data support the further development of these antigens as therapeutic vaccine against Chagas disease.

The role of the Cys23Ser (rs6318) polymorphism of the HTR2C gene in suicidal behavior: systematic review and meta-analysis.

The polymorphisms of the serotonin receptor 2C (HTR2C) gene have been proposed to influence suicidal behavior. The aim of our study was to explore the role of the HTR2C gene variant Cys23Ser (rs6318) in the pathogenesis of suicidal behavior through a systematic review and meta-analysis. The search was performed using EBSCO and PubMed databases. To be included in the analysis, the studies had to evaluate suicidal behavior (attempted, ideation, or completed suicide). The results of the meta-analysis were expressed as odds ratios (ORs). Because HTR2C lies on chromosome X, pooled ORs were calculated, respectively, for each of the models used, namely: allelic, homozygous, dominant, and recessive for the female group and allelic for the male group. The meta-analysis comprised 3867 individuals, including 1668 cases and 2199 controls. The HTR2C Cys23Ser (rs6318) polymorphism did not show a significant association with suicidal behavior either in women (OR: 0.75; 95% confidence interval: 0.55-1.00) or in men (OR: 0.89; 95% confidence interval: 0.64-1.23). Similarly, nonsignificant associations were observed for all of the genetic models used in any of the populations/subgroups studied. Our findings suggest that the rs6318 (Cys23Ser) polymorphism is not associated with suicidal behavior. However, because of the study limitations, we suggest more researches should be performed, increasing the sample sizes and statistical power, to determine the association between the rs6318 variant and suicidal behavior.

Atorvastatin and fenofibrate combination induces the predominance of the large HDL subclasses and increased apo AI fractional catabolic rates in New Zealand white rabbits with exogenous hypercholesterolemia.

The anti-atherogenic properties of high-density lipoproteins (HDLs) may be related to their structure and metabolism. The HDL physicochemical characteristics that determine their plasma clearance during treatment with statins and fibrates are not well understood. In this study, we analyzed HDL-apo AI fractional catabolic rates (FCRs), size distributions, and the lipid composition of the HDL subclasses in New Zealand white rabbits with exogenous dyslipidemia that received low doses of atorvastatin and fenofibrate. Hypercholesterolemia decreased only partially with the combination of both drugs. HDL size distribution shifted toward larger particles among the groups of rabbits that received atorvastatin, fenofibrate, or their combination, compared with both the control group and the dyslipidemic group. The HDL subclasses were significantly rich in cholesterol in each of the groups compared with controls. The structural changes noted in the HDL subclasses were not associated with impaired plasma paraoxonase-1 (PON1) activity. The groups receiving monotherapy and the drug combination group were all associated with a higher apo AI FCR value compared with both the dyslipidemic rabbits and the control group. In conclusion, the combination of atorvastatin and fenofibrate induced a more favorable HDL subclass profile than did the individual use of these drugs. Similarly, the apo AI FCR values were augmented in every group receiving drug treatment (either monotherapy or combination therapy) in the setting of hypercholesterolemia. The anti-atherogenic properties of HDLs, excluding their capacity to bind PON1, may be enhanced by the structural and metabolic modifications induced by the combination of atorvastatin and fenofibrate.

High-resolution HLA analysis of primary and secondary Sjögren's syndrome: a common immunogenetic background in Mexican patients.

To compare the distribution of HLA-A, B, DRB1 and DQB1 alleles among Mexican patients with primary Sjögren Syndrome (pSS), secondary SS (sSS), connective tissue disease (CTD) without (w/o) SS and historical ethnically healthy controls. We included 28 pSS, 30 sSS, 96 CTD w/o SS patients and 234 controls. HLA-A, B, DRB1 and DQB1 were amplified and sequenced using the Allele SEQR Sequenced Based Typing Kits and analyzed on the ABI Prism*3130 DNA Analyzer using the Assign software. Gene frequencies were obtained by direct counting. Contingence tables of 2 × 2 were generated and analyzed by the Mantel-Haenzel χ (2) or Fisher's test (EPIINFO program). We reported odds ratios (OR) and corrected p values. SS patients showed increased frequencies of A*68:01 and DRB1*14:06 alleles when compared to CTD w/o SS (OR 4.43, 95 % CI 1.35-14.14, p = 0.007 and OR 14, 95 % CI 1.68-116, p = 0.001, respectively) and a higher prevalence of DRB1*01:01 (OR 5.9, 95 % CI 2.13-16.56, p = 0.003) and HLA-B*35:01 (OR 3.70, 95 % CI 1.92-7.12, p = 0.004) when compared with controls. pSS patients had a higher frequency of DRB1*14:06 allele than sSS (OR 16, 95 % CI 1.59-390, p = 0.001). Anti-Ro/SSA positivity was associated with B*51:01 (OR 10.11, 95 % CI 1.09-245, p = 0.02) and DRB1*03:01 alleles (OR 4.26, 95 % CI 1.01-18.89, p = 0.029), whereas the A*01:01 allele was associated with anti-La/SSB positivity (OR 4.75, 95 % CI 1.32-16.92, p = 0.003). In our population, the DRB1*14:06 allele was associated with primary and secondary SS implying that both varieties bear a similar immunogenetic background.

Polymorphisms in the promoter region of tumor necrosis factor alpha (TNF-alpha) and the HLA-DRB1 locus in Mexican mestizo patients with ulcerative colitis.

Tumor necrosis factor alpha (TNF-alpha) gene is located within the class III region of the major histocompatibility complex (MHC) on the short arm of the human sixth chromosome. Two polymorphisms in the promoter region of the TNF-alpha gene (-308 and -238) have been associated with the genetic susceptibility to develop ulcerative colitis in both Caucasian and Asian populations. The aim of this study was to determine the role of TNF-alpha gene polymorphisms and those from the HLA-DRB1 locus in the susceptibility to develop ulcerative colitis (UC). Eighty Mexican mestizo patients suffering from UC and 99 ethnically matched unrelated healthy controls were genotyped for two TNF-alpha polymorphisms located in the promoter region (positions -308, -238) by polymerase chain reaction (PCR) and amplification refractory mutation system (ARMS) as well as high resolution DNA typing for HLA-DRB1 alleles were performed. The frequency of individuals positive for allele 2 of the TNF(-308) polymorphism was significantly higher in UC patients than healthy controls (23.7% versus 3%, pC = 0.00002; OR = 10.1; CI 95% = 2.69-26.8). No statistically significant deviation from normality was found between TNF*A (-238) and UC Mexican patients. Clinical manifestations such as pancolitis, extraintestinal manifestations and colectomy were not associated with any of the TNF promoter region polymorphisms. However, HLA-DRB1*15 was found to be associated with pancolitis and HLA-DRB1*0103 with the need of proctocolectomy. In conclusion, this clinical differential pattern of association distinguished in two neighboring loci within the MHC region suggest an independent role of the TNF locus in the genetic susceptibility to develop UC.