Association of TLR8 Variants in Sex-Based Clinical Differences in Patients with COVID-19.

The host immune response might confer differential vulnerability to SARS-CoV-2 infection. The Toll-like receptor 8 (TLR8), could participated for severe COVID-19 outcomes. To investigated the relationship of TLR8 rs3764879-C/G, rs3764880-A/G, and rs3761624-A/G with COVID-19 outcomes and with biochemical parameters. A cross-sectional study of 830 laboratory-confirmed COVID-19 patients was performed, and classified into mild, severe, critical, and deceased outcomes. The TLR8 rs3764879-C/G, rs3764880-A/G, and rs3761624-A/G polymorphisms were genotyped. A logistic regression analysis was performed to determinate the association with COVID-19. A stratified analysis was by alleles was done with clinical and metabolic markets. In all outcomes, men presented the highest ferritin levels compared to women (P < 0.001). LDH levels were significantly different between sex in mild (P = 0.003), severe (P < 0.001) and deceased (P = 0.01) COVID-19 outcomes. The GGG haplotype showed an Odds Ratio of 1.55 (Interval Confidence 95% 1.05-2.32; P = 0.03) in men. Among patients with severe outcome, we observed that the carriers of the GGG haplotype had lower Ferritin, C-reactive protein and LDH levels than the CAA carriers (P < 0.01). After further stratified by sex, these associations were also seen in the male patients, except for D-dimer. Interestingly, among men patients, we could observe associations between TLR8 haplotypes and Ferritin (P < 0.001), D-dimer (P = 0.04), C-reactive protein, and Lactate dehydrogenase in mild (P = 0.04) group. Our results suggest that even though TLR8 haplotypes show a significant association with COVID-19 outcomes, they are associated with clinical markers in COVID-19 severity.

Protective HLA alleles against severe COVID-19: HLA-A*68 as an ancestral protection allele in Tapachula-Chiapas, Mexico.

HLA is a polymorphic antigen presenter which has provided valuable information on the susceptibility of populations to viruses. Therefore, the study of HLA can reveal specific susceptibility or resistance alleles to severe COVID-19 in an ethnically dependent manner. This pilot study investigated HLA alleles associated with COVID-19 severity in Tapachula, Chiapas, Mexico. A total of 146 Mexican Mestizos were typed for HLA class I and II using PCR-SSP. The patients were classified according to the outcome (death or improvement) and the infection's severity (mild or severe). In addition, a group of exposed uninfected individuals was included. HLA-A*68 was found to be a protective allele against the severe infection and fatal outcome; pC = 0.03, OR = 0.4, 95% CI =0.20-0.86, and pC =0.009, OR = 0.3, 95% CI =0.13-0.71 respectively. HLA-DRB1*03 also appears to be a protective factor against fatal outcome pC = 0.009, OR = 0.1, 95%IC = 0.01-0.66; however, the low frequency of this allele in the studied population limits the statistical power. The severity and fatal outcome of COVID-19 patients in Tapachula, Chiapas depend more on the lack of resistance than susceptibility HLA alleles.

Gene expression profiling of inflammatory cytokines in esophageal biopsies of different phenotypes of gastroesophageal reflux disease: a cross-sectional study.

BACKGROUND: The clinical endoscopic phenotypes of gastroesophageal reflux disease (GERD) are classified as Barrett's esophagus (BE), erosive esophagitis (EE) and non-erosive gastroesophageal reflux disease (NERD). NERD is subclassified as abnormal acid exposure (AAE) and normal acid exposure (NAE) based on pH monitoring study results. The aim of this study was to characterize genes involved in the pathophysiology and immune response of GERD. METHODS: This is an observational and cross-sectional study. All patients with BE, EE, AAE, and NAE and a control group were subjected to superior endoscopy (with biopsies of esophageal mucosa). Relative mRNA quantification of cytokine and target genes was conducted by quantitative Polymerase Chain Reaction (RT-qPCR). Changes in the expression of genes associated with inflammation were assessed for each disease phenotype. Statistical analysis of differential gene expression was performed using the Mann-Whitney U non-parametric test. A p value < 0.05 was considered significant. RESULTS: A total of 82 patients were included and were divided into the following groups: Group BE, 16 (19.51%); Group EE, 23 (28.04%); Group AAE, 13 (15.86%); NAE 13 (15.86%); and Control Group, 17 (20.73%). Compared with the control group, patients with BE exhibited increased IL-8 expression (p < 0.05) and increased levels of IL-10, MMP-3, and MMP-9. Patients with EE exhibited increased levels of IL-1B, IL-6 and IL-10 (p < 0.05), and patients with AAE exhibited increased expression of IL-1B, IL-6, IFN-γ and TNF-α (p < 0.05). AAE exhibited increased IL-1B and TNF-α expression compared with NAE (p < 0.05). CONCLUSION: This study demonstrates the differential expression of mediators of inflammation in the esophageal mucosa of patients with different GERD endoscopic phenotypes. IL-1B and TNF-α could be useful to differentially diagnose AAE and NAE in the non-erosive phenotype using endoscopic biopsies.

Analysis of CYP450 gene allelic variants can predict ifosfamide toxicity in Mexican paediatric patients.

Context: Ifosfamide (IFA) is an effective antineoplastic for solid tumours in children, although it is associated with high levels of systemic toxicity and causes death in some cases. Objective: The aim of this study was to determine whether the presence of certain allelic variants of genes CYP2B6, CYP2C9, CYP3A4 and CYP3A5 increases the risk of toxicity in children with solid tumours treated with ifosfamide.Materials and methods: A total of 131 DNA samples were genotyped by real-time polymerase chain reaction (RT-PCR) using TaqMan probes. Toxicity was assessed using WHO criteria, and survival analysis was performed using Kaplan-Meier curves.Results: The rs3745274 allelic variant in CYP2B6 was associated with haematological toxicity, affecting neutrophils; CYP3A4 variant rs2740574 was also associated with toxicity, affecting both leukocytes and neutrophils. Additionally, the CYP3A5 gene variant rs776746 was found to affect haemoglobin.Conclusions: Our results show that allelic variants rs3745274 (CYP2B6), rs2740574 (CYP34) and rs776746 (CYP3A5) increase the risk for high haematological toxicity.Clinical trial registration: 068/2013.

An Isolated TCR αß Restricted by HLA-A*02:01/CT37 Peptide Redirecting CD8+ T Cells To Kill and Secrete IFN-γ in Response to Lung Adenocarcinoma Cell Lines.

Lung cancer is a leading cause of cancer-related death among both men and women in the United States, where non-small cell lung cancer accounts for ∼85% of lung cancer. Lung adenocarcinoma (ADC) is the major histologic subtype. The presence of actionable mutations prompts the use of therapies designed to specifically address the deleterious effects of those cancer-driving mutations; these therapies have already shown promise in cases carrying those actionable mutations (∼30%). Innovative therapeutic approaches are needed for the treatment of 70% of patients suffering from lung ADC. Adoptive transfer of CD8+ T cells specific against cancer/testis (CT) Ags, whose protein expression is restricted to the gonads (testis and ovary) and cancerous cells, is an excellent alternative. In this study, we report the isolation of HLA-A*02:01/CT37 peptide-specific α and ß TCR chains from a CD8+ T cell clone obtained from a patient suffering from lung ADC. We also report the development of an innovative CD3ζ construct. With those TCR chains and the engineered (modified) CD3ζ chain, we produced a construct that when transduced into CD8+ T cells is capable of redirecting transduced CD8+ T cell cytotoxic activity and IFN-γ secretion against peptide-pulsed autologous cells and HLA-A*02:01-positive and CT37-expressing lung ADC cell lines. Our findings will launch the development of innovative adoptive transfer immunotherapies for the treatment of lung ADC, targeting the most prevalent HLA molecules and CT37 peptides restricted by these molecules.

Investigation of an Immunogenetic Profile in Patients with Abdominal Aortic Aneurysms and Possible Applications in Screening and Surveillance.

BACKGROUND: The pathogenesis of atherosclerotic abdominal aortic aneurysms (AAAs) remains not fully understood. Histological analyses confirm chronic adventitial and medial inflammatory cell infiltration, and its pathophysiology involves the upregulation of proteolytic pathways; added to this, genetic factors have been suggested to favor the susceptibility for AAA. The aim of the present study was to analyze the association between genetic polymorphism of the class II human leukocyte antigens (HLAs, HLA-DRB1) with the susceptibility to develop AAA in Mexican patients and to initiate a pilot study of single-nucleotide polymorphisms (SNPs) rs1024611 in the monocyte chemoattractant protein-1 (MCP-1/CCL2) gene to investigate a possible role in the AAA pathogenesis. METHODS: In a cohort of patients with AAA, HLA molecular typing was completed for DRB1 loci with LABType SSO-One Lambda kit in 39 patients (69% men with a mean age of 72 years) and compared with 99 without the disease (60% men, mean age 65 years) (control group). Genotyping of rs1024611 in the MCP-1 gene was performed using TaqMan predesigned SNP genotyping assays in 27 patients with AAA (63% men, mean age of 71). Gene frequencies (gfs) and genotype frequencies (Gfs) were determined; categorical data were analyzed by nonparametric statistic test at significance level (P < 0.05), and odds ratios (ORs) were calculated using the STATA v14 software and StatCalc software Epi Info™ 7.2.2.2. RESULTS: Seventy-eight HLA-DRB1 alleles of patients with AAA and 198 from the control group were studied. We observed that the gf of HLA-DRB1*01 was 0.128 in the AAA group compared with 0.05 in the control group (P = 0.03, OR: 2.6, 95% confidence interval [CI]: 1.04-6.5); the gf of HLA-DRB1*16 was 0.115 in the AAA and 0.025 in control group (P = 0.002, OR: 5, 95% CI: 1.6-16.9). The Gf for SNP rs1024611 were 0.51 in the GA genotype, 0.30 in AA, and 0.19 of GG. Four patients with the proinflammatory homozygous genotype GG (80%) were women and younger than patients with other genotypes, and only one had a history of dyslipidemia. CONCLUSIONS: The dissection and interpretation of an immunogenetic profile in patients with AAA is an active and complex field of research that might assist in a more precise identification of those patients at genetic risk. Our study demonstrated increased frequencies of HLA-DRB1*01 and HLA-DRB1*16 alleles in Mexican patients with AAA compared with an ethnically matched control group.

Effect of 15 BMI-Associated Polymorphisms, Reported for Europeans, across Ethnicities and Degrees of Amerindian Ancestry in Mexican Children.

In Mexico, the genetic mechanisms underlying childhood obesity are poorly known. We evaluated the effect of loci, known to be associated with childhood body mass index (BMI) in Europeans, in Mexican children from different ethnic groups. We performed linear and logistic analyses of BMI and obesity, respectively, in Mestizos and Amerindians (Seris, Yaquis and Nahuatl speakers) from Northern (n = 369) and Central Mexico (n = 8545). We used linear models to understand the effect of degree of Amerindian ancestry (AMA) and genetic risk score (GRS) on BMI z-score. Northern Mexican Mestizos showed the highest overweight-obesity prevalence (47.4%), followed by Seri (36.2%) and Central Mexican (31.5%) children. Eleven loci (SEC16B/rs543874, OLFM4/rs12429545/rs9568856, FTO/rs9939609, MC4R/rs6567160, GNPDA2/rs13130484, FAIM2/rs7132908, FAM120AOS/rs944990, LMX1B/rs3829849, ADAM23/rs13387838, HOXB5/rs9299) were associated with BMI and seven (SEC16B/rs543874, OLFM4/rs12429545/rs9568856, FTO/rs9939609, MC4R/rs6567160, GNPDA2 rs13130484, LMX1B/rs3829849) were associated with obesity in Central Mexican children. One SNP was associated with obesity in Northern Mexicans and Yaquis (SEC16B/rs543874). We found higher BMI z-score at higher GRS (ß = 0.11, p = 0.2 × 10-16) and at lower AMA (ß = -0.05, p = 6.8 × 10-7). The GRS interacts with AMA to increase BMI (ß = 0.03, p = 6.08 × 10-3). High genetic BMI susceptibility increase the risk of higher BMI, including in Amerindian children.

Association of the PSRC1 rs599839 Variant with Coronary Artery Disease in a Mexican Population.

Background and Objectives: Coronary artery disease (CAD) is a major health problem in México. The identification of modifiable risk factors and genetic biomarkers is crucial for an integrative and personalized CAD risk evaluation. In this work, we aimed to validate in a Mexican population a set of eight selected polymorphisms previously associated with CAD, myocardial infarction (MI), or dyslipidemia. Materials and Methods: A sample of 907 subjects (394 CAD cases and 513 controls) 40-80 years old was genotyped for eight loci: PSRC1 (rs599839), MRAS (rs9818870), BTN2A1 (rs6929846), MTHFD1L (rs6922269), CDKN2B (rs1333049), KIAA1462 (rs3739998), CXCL12 (rs501120), and HNF1A (rs2259816). The association between single nucleotide polymorphisms (SNPs) and CAD was evaluated by logistic regression models. Results: Multiple logistic regression analysis with adjustment by age, gender, and body mass index showed that rs599839 was significantly associated with CAD (ORADD = 0.72, p = 0.009; ORDOM = 0.66, p = 0.007). Conclusions: The PSRC1 rs599839 polymorphism shows a significant protective association with CAD in this sample of the Mexican population.

Genetic polymorphism of HLA-DRB1 alleles in Mexican mestizo patients with abdominal aortic aneurysms.

BACKGROUND: Multiple factors are implicated in the etiology and pathogenesis of Abdominal Aortic Aneurysms (AAA). Available literature of genetic studies has previously suggested the possible roles of autoimmunity, genetic predisposition and ethnic susceptibility. Due to the association with autoimmune diseases and proven application in population genetics, we aimed to investigate alleles of the Class II Human Leukocyte Antigens (HLA-DRB1) in the Mexican Mestizo population with aortic aneurysms and determine possible associations with susceptibility. METHODS: We performed a case Control Study; the HLA molecular typing was completed for DRB1 loci by LabType Sequence-Specific Oligonucleotide (SSO) SSO-OneLambda kit (Applied Biosystems; Thermo Fisher Scientific. Inc.) in the studied individuals. Allele frequencies (af) were determined, associations were assessed by chi square or fisher exact tests at significance level (< 0.05), and Odds Ratios (OR) were calculated using the STATA software version 14. RESULTS: The genetic polymorphism of HLA-DRB1 of fifty one patients (70% males with a mean age of 71 years) with atherosclerotic or also known as degenerative AAA were compared with 99 unrelated patients (60% males, mean age 65 years) without the disease [Control group (CG)] from the same ethnic group. We examined a total of 102 Class II HLA-DRB1 alleles of AAA patients and 198 from CG. When comparing af, we observed the HLA-DRB1*01 af of 0.139 in the AAA compared to 0.05 in the CG [p = 0.015, OR 3, 95% confidence interval (CI) 1.29-7.08], the HLA-DRB1*16 af were 0.109 in the AAA and 0.025 in CG (p = 0.006, OR 4.7, 95% CI 1.59-13.98). CONCLUSIONS: Our study confirmed increased frequencies of the alleles HLA-DRB1*01 and HLA-DRB1*16 and their association to the development of AAA in Mexican Mestizo patients. The utility of genetic testing may assist in identifying individuals at genetic risk for the development of this disease in different ethnic groups, who might benefit from earlier ultrasound screening and closer imaging surveillance.

Effect of multi-component school-based program on body mass index, cardiovascular and diabetes risks in a multi-ethnic study.

BACKGROUND: Mexico occupies one of the first places worldwide in childhood obesity. Its Mestizo and Indigenous communities present different levels of westernization which have triggered different epidemiological diseases. We assessed the effects of a multi-component school-based intervention program on obesity, cardiovascular and diabetes risk factors. METHODS: A physical activity, health education and parent involvement (PAHEPI) program was developed and applied in six urban (Mestizo ethnic group) and indigenous (Seri and Yaqui ethnic groups) primary schools for 12 weeks. A total of 320 children aged 4-12 years participated in intervention program; 203 under Treatment 1 (PAHEPI program) and 117, only from Mestizo groups, under Treatment 2 (PAHEPI+ school meals). For Body Mass Index (BMI), cardiovascular and diabetes factors, pairwise comparisons of values at baseline and after treatments were done using Wilcoxon signed rank test. Generalized linear models were applied to assess the intervention effect by age, sex and nutritional status in relation to ethnicity and treatment. RESULTS: We observed improvements on BMI in children with overweight-obesity and in triglycerides in the three ethnic groups. The Mestizo ethnic group showed the largest improvements under Treatment 2. While Seris showed improvements only in cardiovascular risk factors, Yaquis also showed improvements in diabetes risk factors, though not in BMI. CONCLUSIONS: This study showed that the same intervention may have positive but different effects in different ethnic groups depending on their lifestyle and their emerging epidemiological disease. Including this type of intervention as part of the school curriculum would allow to adapt to ethnic group in order to contribute more efficiently to child welfare. TRIAL REGISTRATION: This study was retrospectively registered under the identifier NCT03768245 .

Common Polymorphisms Linked to Obesity and Cardiovascular Disease in Europeans and Asians are Associated with Type 2 Diabetes in Mexican Mestizos.

Background and objectives: Type 2 diabetes (T2D) is a major problem of public health in Mexico. We investigated the influence of five polymorphisms, previously associated with obesity and cardiovascular disease in Europeans and Asians, on T2D in Mexican Mestizos. Materials and Methods: A total of 1358 subjects from 30 to 85 years old were genotyped for five loci: CXCL12 rs501120; CDNK2A/B rs1333049; HNF-1α rs2259816; FTO rs9939609; and LEP rs7799039. We used logistic regressions to test the effect of each locus on T2D in two case⁻control groups with obesity and without obesity. Also, linear regression models on glucose and glycated hemoglobin (HbA1c) were carried out on the whole sample, adjusted by age, gender, and body mass index. Results: The CXCL12 rs501120 C allele (OR = 1.96, p = 0.02), the FTO rs9939609 A allele (OR = 2.20, p = 0.04) and the LEP rs7799039 A allele (OR = 0.6, p = 0.03) were significantly associated with T2D in obesity case⁻control group. No significant association was found in the non-obesity case⁻control group. The linear regression model showed that CDNK2A/B rs1333049 C allele (ß = 0.4, p = 0.03) and FTO rs9939609 A allele (ß = 0.5, p = 0.03), were significantly associated with HbA1c, but no association was found among the loci with the glucose levels. Conclusions: Polymorphisms previously linked with obesity and cardiovascular events were also associated with T2D and high levels of HbA1c. Furthermore, we must point at the fact that this is the first report where polymorphisms CXCL12 rs501120 and LEP rs7799039 are associated with T2D in subjects with obesity.

Frequency of the T307A, N680S, and -29G>A single-nucleotide polymorphisms in the follicle-stimulating hormone receptor in Mexican subjects of Hispanic ancestry.

BACKGROUND: FSHR SNPs may influence the ovarian sensitivity to endogenous and exogenous FSH stimulation. Given the paucity of data on the FSHR c.919A > G, c.2039A > G and - 29G > A SNPs in Hispanic population, we here analyzed their frequency distribution in Mexican mestizo women. METHODS: Samples from 224 Mexican mestizo women enrolled in an IVF program as well as a genotype database from 8182 Mexican mestizo subjects, were analyzed for FSHR SNPs at positions c.919, c.2039 and - 29G > A. Association between the genetic variants and reproductive outcomes was assessed. RESULTS: The c.919 and c.2039 SNPs were in strong linkage disequilibrium and their corresponding genotype frequencies in the IVF group were: AA 46.8%, AG 44.2%, and GG 8.9%, and AA 41.9%, AG 48.2% and GG 9.8%, respectively. For the -29G > A SNP, genotype frequencies were 27% (GG), 50% (GA) and 23% (AA). In normal oocyte donors with the c.2039 GG genotype, the number of oocytes recovered after ovarian stimulation (COS) were significantly (p < 0.01) lower than in those bearing other genotypes in this or the -29G > A SNP. Analysis of the large scale database revealed that both allelic and genotype frequencies for the three SNPs were very similar to those detected in the IVF cohort (p ≥ 0.38) and that female carriers of the c.2039 G allele tended to present lower number of pregnancies than women bearing the AA genotype; this trend was stronger when women with more Native American ancestry was separately analyzed (OR = 2.0, C.I. 95% 1.03-3.90, p = 0.04). There were no differences or trends in the number of pregnancies among the different genotypes of the -29G > A SNP. CONCLUSIONS: The frequency of the GG/GG combination genotype for the c.919 and c.2039 SNPs in Mexican hispanics is among the lowest reported. The GG genotype is associated with decreased number of oocytes recovered in response to COS as well as to lower pregnancy rates in Hispanic women from the general population. The absence of any effect of the -29AA genotype on the response to COS, indicates that there is no need to perform this particular genotype testing in Hispanic women with the purpose of providing an individually-tailored COS protocol.

The association of AKNA gene polymorphisms with knee osteoarthritis suggests the relevance of this immune response regulator in the disease genetic susceptibility.

Recent studies have identified AKNA as a potential susceptibility gene for several inflammatory diseases. Here, we aimed to assess the potential association of AKNA polymorphisms with knee osteoarthritis (KOA) susceptibility in a Mexican population, following STREGA recommendations. From a DNA bank of 181 KOA patients and 140 healthy controls, two AKNA SNPs were genotyped using TaqMan probes. The association between KOA susceptibility and AKNA polymorphisms genotypes was evaluated by multivariated logistic regression analysis. Information regarding patients' inflammatory biomarkers levels was obtained and their association with AKNA polymorphisms genotypes was assessed by lineal regression. We found a positive association with the recessive inheritance model of both AKNA polymorphisms (A/A genotype for both) and KOA susceptibility adjusting by age, body mass index (BMI), gender and place of birth (OR = 2.48, 95% CI 1.09-5.65 for rs10817595 polymorphism; and OR = 4.96; 95% CI 2.421-10.2 for rs3748176 polymorphism). Additionally these associations were also seen after stratifying patients by KOA severity and age. Furthermore the total leukocyte count was positively associated with rs10817595 AKNA polymorphism (ß = 1.39; 95% CI 0.44-2.34) adjusting by age, BMI, gender, place of birth and disease severity. We suggest that regulatory and coding polymorphisms of the inflammatory modulator gene AKNA can influence the development of KOA. Further structural and functional studies might reveal the role of AKNA in OA and other rheumatic diseases.

Fast Morphological Gallbladder Changes Triggered by a Hypercholesterolemic Diet.

INTRODUCTION AND AIM: Obesity is a worldwide epidemic problem, described as a risk factor for hepatic diseases, such as non-alcoholic fatty liver disease and other pathologies related to development of cholesterol crystals and cholesterol gallbladder stones. It has been reported that cholesterol overload may cause hepatic damage; however, little is known about the effects of an acute hypercholesterolemic diet on the gallbladder. The aim of this manuscript was to evaluate the impact of a cholesterol-rich diet on the gallbladder. MATERIAL AND METHODS: The study included ten eight-week-old C57BL6 male mice, which were divided into two study groups and fed different diets for 48 h: a hypercholesterolemic diet and a balanced Chow diet. After 48 h, the mice were analyzed by US with a Siemens Acuson Antares equipment. Mice were subsequently sacrificed to carry out a cholesterol analysis with a Refloton System (Roche), a crystal analysis with a Carl Zeiss microscope with polarized light, and a histological analysis with Hematoxylin-eosin staining. RESULTS: The hypercholesterolemic diet induced an increase in gallbladder size and total cholesterol content in the bile, along with important histological changes. CONCLUSION: Cholesterol overloads not only trigger hepatic damage, but also affect the gallbladder significantly.

Vaccination Recommendations for Adults With Autoimmune Inflammatory Rheumatic Diseases in Latin America.

BACKGROUND/OBJECTIVE: Patients with autoimmune inflammatory rheumatic diseases (AIRDs) are at increased risk of contracting severe infections and suffering complications, particularly when they are receiving immunomodulating therapy. Vaccination is an important means to prevent many potential infections and thereby reduce the morbidity and mortality associated with AIRD. The purpose of this consensus document is to provide health care professionals with recommendations for the vaccination of AIRD patients who reside in Latin America. The recommendations were developed by an expert committee from the region based on a review of the literature and their clinical experience. METHODS: The Americas Health Foundation (AHF) used PubMed and EMBASE to identify clinicians and scientists with an academic or hospital affiliation and who had published in the field of adult vaccination and rheumatic diseases since 2010. As a result of this effort, AHF convened an 8-member panel of clinical and scientific experts from Latin America. Both the AHF and panel members conducted a careful literature review to identify relevant publications in the areas of adult vaccination and rheumatology, and the sum of the articles identified was provided to the entire panel. Prior to the conference, panelists were each asked to prepare a written response to a salient issue on the subject, identified by AHF. RESULTS AND CONCLUSIONS: During the conference, each response was edited by the entire group, through numerous drafts and rounds of discussion until a complete consensus on vaccination recommendations for adult patients with AIRDs was obtained, including 7 key recommendations.

Genetic Obesity Risk and Attenuation Effect of Physical Fitness in Mexican-Mestizo Population: a Case-Control Study.

We analyzed commonly reported European and Asian obesity-related gene variants in a Mexican-Mestizo population through each single nucleotide polymorphism (SNP) and a genetic risk score (GRS) based on 23 selected SNPs. Study subjects were physically active Mexican-Mestizo adults (n = 608) with body mass index (BMI) values from 18 to 55 kg/m2 . For each SNP and for the GRS, logistic models were performed to test for simple SNP associations with BMI, fat mass percentage (FMP), waist circumference (WC), and the interaction with VO2max and muscular endurance (ME). To further understand the SNP or GRS*physical fitness components, generalized linear models were performed. Obesity risk was significantly associated to 6 SNPs (ADRB2 rs1042713, APOB rs512535, PPARA rs1800206, TNFA rs361525, TRHR rs7832552 and rs16892496) after adjustment by gender, age, ancestry, VO2max , and ME. ME attenuated the influence of APOB rs512535 and TNFA rs361525 on obesity risk in FMP. WC was significantly associated to GRS. Both ME and VO2max attenuated GRS effect on WC. We report associations for 6 out of 23 SNPs and for the GRS, which confer obesity risk, a novel finding for Mexican-Mestizo physically active population. Also, the importance of including physical fitness components variables in obesity genetic risk studies is highlighted, with special regard to intervention purposes.

HLA Alleles are Genetic Markers for Susceptibility and Resistance towards Leprosy in a Mexican Mestizo Population.

Despite the use of multidrug therapy, leprosy remains endemic in some countries. The association of several human leucocyte antigen (HLA) alleles and gene polymorphisms with leprosy has been demonstrated in many populations, but the major immune contributors associated to the spectrum of leprosy have not been defined yet. In this study, genotyping of HLA-A, -B, -DR, and -DQ alleles was performed in leprosy patients (n = 113) and control subjects (n = 117) from the region with the highest incidence for the disease in México. The odds of developing leprosy and lepromatous subtype were 2.12- and 2.74-fold higher in carriers of HLA-A*28, and 2.48- and 4.14-fold higher for leprosy and dimorphic subtype in carriers of DQB1*06. Interestingly, DQB1*07 was overrepresented in healthy individuals, compared to patients with leprosy (OR = 0.08) and the lepromatous subtype (OR = 0.06). These results suggest that HLA-A*28 is a marker for predisposition to leprosy and the lepromatous subtype and DQB1*06 to leprosy and the dimorphic subtype, while DQB1*07 might be a resistance marker in this Mestizo population.

Genetic Differentiation in a Sample from Northern Mexico City Detected by HLA System Analysis: Impact in the Study of Population Immunogenetics.

The major histocompatibility complex is directly involved in the immune response, and thus the genes coding for its proteins are useful markers for the study of genetic diversity, susceptibility to disease (autoimmunity and infections), transplant medicine, and pharmacogenetics, among others. The polymorphism of the system also allows researchers to use it as a proxy for population genetics analysis, such as genetic admixture and genetic structure. In order to determine the immunogenetic characteristics of a sample from the northern part of Mexico City and to use them to analyze the genetic differentiation from other admixed populations, including those from previous studies of Mexico City population, we analyzed molecular typing results of donors and patients from the Histocompatibility Laboratory of the Central Blood Bank of the Centro Médico Nacional La Raza selected according to their geographic origin. HLA-A, -B, -DRB1, and -DQB1 alleles were typed by polymerase chain reaction with sequence-specific primers. Allelic and haplotype frequencies, as well as population genetics parameters, were obtained by maximum likelihood methods. The most frequent haplotypes found were HLA-A*02/-B*39/-DRB1*04/-DQB1*03:02P, HLA-A*02/-B*35/-DRB1*04/-DQB1*03:02P, HLA-A*68/-B*39/-DRB1*04/-DQB1*03:02P, and HLA-A*02/-B*35/-DRB1*08/-DQB1*04. Importantly, the second most frequent haplotype found in our sample (HLA-A*02/-B*35/-DRB1*04/-DQB1*03:02P) has not been previously reported in any mixedancestry populations from Mexico but is commonly encountered in Native American human groups, which can reflect the impact of migration dynamics in the genetic conformation of the northern part of Mexico City, and the limitations of previous studies with regard to the genetic diversity of the analyzed groups. Differences found in haplotype frequencies demonstrated that large urban conglomerates cannot be analyzed as one homogeneous entity but, rather, should be understood as a set of structures in which social, political, and economical factors influence their genesis and dynamics.

Characterization of complete mitochondrial genomes of indigenous Mayans in Mexico.

BACKGROUND: The authors have previously published the complete mitochondrial genome (mitogenome) sequences of two indigenous Mesoamerican populations, Mazahua (n = 25) and Zapotec (n = 88). METHODS: This study determined the complete mitogenome sequences of nine unrelated individuals from the indigenous Maya population living in Mexico. RESULTS: Their mitogenome sequences could be classified into either of the haplogroups A2 and C1. Surprisingly, there were no mitogenome sequences (haplotypes) that the Maya, Mazahua, and Zapotec people share in common. CONCLUSIONS: This indicates that no genetic exchange, at least matrilineally, has occurred among them.

Pretransplant angiotensin II type 1-receptor antibodies are a risk factor for earlier detection of de novo HLA donor-specific antibodies.

BACKGROUND: Angiotensin II type 1 receptor antibodies (AT1Rabs) have been associated with significantly reduced graft survival. Earlier graft loss has been observed in patients who had pretransplant AT1Rabs and posttransplant donor-specific antibodies (DSA). METHODS: The main goal of this retrospective cohort study was to examine the association between AT1Rabs and the time period to detection of de novo human leukocyte antigen (HLA-DSA) posttransplantation in living donor kidney transplant recipients (KTR). The analysis included 141 KTRs. Pretransplant frozen serum samples were tested for AT1Rabs by ELISA and HLA-DSA by SAB (Luminex) at both the pre- and post-KT time points. RESULTS: The median AT1Rab level was 9.13 U (interquartile range 5.22-14.33). After a mean follow-up period of 3.55 years, 48 patients were found to harbour de novo HLA-DSAs. The presence of AT1Rabs [hazard ratio (HR) 1.009, 95% confidence interval (CI) 1.002-1.01, P = 0.010], male-to-male transplantation (HR 2.57, 95% CI 1.42-4.67, P = 0.002) and antecedent borderline changes or acute cellular rejection (ACR) (HR 2.47, 95% CI 1.29-4.75, P = 0.006) were significantly associated with de novo DSA detection. A dose-dependent association between AT1Rab levels (<10 U, 10.1-16.9 U, 17-29.9 U and >30 U) and de novo DSA detection was observed (log-rank P = 0.0031). After multivariate analysis of AT1Rab levels (continuous variable), AT1Rabs >30 U, male-to-male transplantation, donor age, higher class I percentage of Panel Reactive Antibody and antecedent borderline changes or ACR remained as independent significant risk factors for the detection of de novo DSAs. CONCLUSIONS: The findings suggest that higher levels of pretransplant circulating antibodies against AT1R (>30 U) in kidney graft recipients constitute an independent risk factor for earlier de novo HLA-DSA detection during the posttransplant period.