Presence of human adenovirus 36 in visceral fat tissue, viral load, and analysis of its genetic variability.

It has been proposed that infection by adipogenic viruses constitutes a "low risk" factor for obesity. Here, we report the presence of adenovirus 36 (Ad36) and its viral load copy number in fat tissue of participants with obesity and normal weight; phylogenetic analysis was performed to describe their relationship and genetic variability among viral haplotypes. Adipose tissue obtained from 105 adult patients with obesity (cases) and 26 normal-weight adult participants as controls were analyzed by quantitative polymerase chain reaction (qPCR) amplifying the partial Ad36 E1a gene. The amplicons were examined by melting curves and submitted to sequencing. Then, genetic diversity and phylogenetic inferences were performed. Ad36 was identified at rates of 82% and 46% in the case and control groups, respectively (p = 1.1 × 10-4 , odds ratio = 5.28); viral load copies were also significantly different between both groups, being 25% higher in the case group. Melting curve analysis showed clear amplification among positive samples. Phylogenetic inferences and genetic diversity analyses showed that the Ad36 E1a gene exhibits low genetic variability and differentiation with strong gene flow due to an expanding process. Our results suggest that the phenomenon of infectobesity by Ad36 might not be a low-risk factor, as has been previously argued by other authors.

Human Leukocyte Antigens -DQA1 and -DQB1 Alleles in Patients With Common Warts.

Introduction The human papillomavirus induces the formation of lesions in different epithelia. Several studies describe an association of class II human leukocyte antigen with genital lesions, implying that they could also be related to the presence of common warts. The goal of this work was to determine the frequency of human leukocyte antigens (HLA)-DQA1 and HLA-DQB1 in Mexicans with common warts. Methods Thirty-two patients with a diagnosis of common warts, without any other systemic disease, and 100 healthy subjects from the same geographic area were recruited. The second exon of the HLA-DQA1 and HLA-DQB1 loci was typed by dot-blot and chemiluminescence. Results Alleles DQA1*03:01:01 (P = 0.021) and DQB1*03:02 (P = 0.036) were associated with the presence of skin warts. DQA1*04:01-DQB1*04:02 (P = 0.009) and DQA1*03:01:01-DQB1*03:02 (P = 0.044) were the most frequent haplotypes in patients. Conclusion In conclusion, the results of our study showed that the alleles DQA1 *03:01:01, DQB1*03:02, DQA1 *04:01, and DQB1*04:02 were associated with susceptibility to common warts, while DQA1*05:01 was significantly diminished in them. Consequently, the haplotypes DQA1*04:01-DQB1*04: 02 and DQA1*03:01:01-DQB1*03:02 were found to be associated with susceptibility, and DQA1*05:01-DQB1*03:01 increased significantly in controls. Therefore, the alleles of the DQA1 and DQB1 genes that are associated with susceptibility could be presenting human papillomavirus (HPV) peptides to T lymphocytes that activate a Th2-type response (anti-inflammatory cytokines), which allows the development of skin warts in this population.

Association between cycle threshold (Ct ) values and clinical and laboratory data in inpatients with COVID-19 and asymptomatic health workers.

In-house assays for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), are feasible alternatives, particularly in developing countries. Cycle threshold (Ct ) values obtained by qRT-PCR were compared with clinical and laboratory data from saliva of inpatients with COVID-19 and asymptomatic health workers (AHW) were studied. Saliva specimens from 58 inpatients confirmed by qRT-PCR for SARS-CoV-2 using nasopharyngeal specimens, and 105 AHW were studied by qRT-PCR using three sets of primers for the N (N1, N2, and N3) gene of SARS-CoV-2, according to the CDC Diagnostic Panel protocol, showing a positivity of 88% for inpatients and 8% for AHW. Bivariate analysis revealed an association between Ct < 38.0 values for N2 and mechanical ventilation assistance among patients (p = .013). In addition, values of aspartate-transaminase, lactate dehydrogenase, and ferritin showed significant correlations with Ct values of N1 and N3 genes in inpatients. Therefore, our results show that Ct values correlate with some relevant clinical data for inpatients with COVID-19.

Cervical lymph node tuberculosis and TNF, IL8, IL10, IL12B and IFNG polymorphisms.

Cervical lymph node tuberculosis (LNTB) is the most common manifestation of extrapulmonary tuberculosis, resulting from the interaction of environmental and genetic factors. The immune response against TB is regulated by several cytokines, which have single nucleotide polymorphisms (SNPs), leading to different levels of expression. The aim of this study was to evaluate the association of LNTB with the TNF, IL8, IL10, IL12B and IFNG gene polymorphisms in Mexican patients. We investigated the association of ten SNPs in 14 patients with LNTB and 138 healthy controls. Significant differences were found for the allele TNF-238A (P=0.03) and the genotypes TNF-238GA (P=0.03), IL8+396GG (P=0.01) and IL12B+1188CC (P=0.04). Allele IL8+781C showed some association trend (P=0.08). Haplotypes TNF-AA and IL10-GTA were of susceptibility, whereas haplotype IL8-ATT was of protection. No association was found with IFNG. The association of these polymorphisms with extrapulmonary TB was compared in different populations. Our results suggest that these cytokine SNPs may influence the manifestation of LNTB in Mexican patients; however, we are aware of the limitations of our study, so it is necessary to make a replica using a larger sample of patients, as well as an increased number of cytokines with SNPs.

Clinical study and some molecular features of Mexican patients with syndromic craniosynostosis.

BACKGROUND: Craniosynostosis is one of the major genetic disorders affecting 1 in 2,100-2,500 live newborn children. Environmental and genetic factors are involved in the manifestation of this disease. The suggested genetic causes of craniosynostosis are pathogenic variants in FGFR1, FGFR2, FGFR3, and TWIST1 genes. METHODS: In order to describe their major clinical characteristics and the presence of pathogenic variants, a sample of 36 Mexican patients with craniosynostosis diagnosed as: Crouzon (OMIM 123,500), Pfeiffer (OMIM 101,600), Apert (OMIM 101,200), Saethre-Chotzen (OMIM 101,400), and Muenke (OMIM 602,849) was analyzed. RESULTS: In addition to craniosynostosis, most of the patients presented hypertelorism, midface hypoplasia, and abnormalities in hands and feet. To detect the pathogenic variants p.Pro252Arg FGFR1 (OMIM 136,350), p.Ser252Trp, p.Pro253Arg FGFR2 (OMIM 176,943), p.Pro250Arg, FGFR3 (OMIM 134,934), and p.Gln119Pro TWIST1 (OMIM 601,622), PCR amplification and restriction enzyme digestion were performed. Four and two patients with Apert presented the pathogenic variants p.Ser252Trp and p.Pro253Arg in FGFR2, respectively (with a frequency of 11.1% and 5.5%). The p.Pro250Arg pathogenic variant of FGFR3 was found in a patient with Muenke (with a frequency of 2.8%). The above percentages were calculated with the total number of patients. CONCLUSION: The contribution of this work is discreet, since only 4 genes were analyzed and sample size is small. However, this strategy could be improved by sequencing the FGFR1, FGFR2, FGFR3, and TWIST1 genes, to determine different pathogenic variants. On the other hand, it would be important to include other genes, such as TCF12 (OMIM 600,480), MSX2 (OMIM 123,101), RAB23 (OMIM 606,144), and EFNB1 (OMIM 300,035), to determine their participation in craniosynostosis in the Mexican population.

MSX1 gene polymorphisms in Mexican patients with non-syndromic cleft lip/palate.

OBJECTIVE: Non-syndromic cleft lip/palate malformation (CL/P) is one of the most common birth defects in humans and has a complex etiology involving genetic and environmental factors. Mutations in the MSX1 gene are critical during craniofacial development. The purpose of this study was to investigate the contribution of MSX1 gene polymorphisms to the risk of developing CL/P in a sample of Mexican patients. METHODS: The sample consisted of 282 subjects (69 cases and 213 relatives). Four single-nucleotide polymorphisms (SNP1, P147Q, SNP5 and P278S) were tested for association with CL/P in triad and case-pseudo-control analyses. Polymorphism typing was performed by restriction fragment length polymorphism and dot-blot techniques. Allele and genotype frequencies were calculated between patients and pseudo-controls and compared using the Chi square test with Yates correction. Odds ratios and 95% confidence intervals were obtained using SPSS software (v19). Triad analysis was also performed using the program HAPLIN (v5.3). RESULTS: In the cases and pseudo-controls, an association was found between CL/P and the SNP1-G allele (P = 0.031) and the SNP1-G/G genotype (P = 0.032), a polymorphism located near MSX1. Triad analysis showed a tendency toward CL/P susceptibility for the genotype SNP1-G/G (P = 0.075) and an association between CL/P and the haplotype GCTC (P = 0.037). No associated haplotype was found in the cases and pseudo-controls. Two partial haplotypes, GT (SNP1-SNP5) (P = 0.032) and GC (SNP1-P278S) (P = 0.033), were associated with susceptibility in the heterozygous and homozygous types, respectively. In contrast, haplotype AT (SNP1-SNP5) was associated with protection (P = 0.012) in the homozygous type. CONCLUSIONS: The results of this study suggest an association between CL/P susceptibility and SNP1, located near the MSX1 gene, in the Mexican population.

IRF6 polymorphisms in Mexican patients with non-syndromic cleft lip.

Cleft lip with or without cleft palate (CL/P) is one of the most common birth defects; it is a multifactorial disease affecting > 1/1,000 live births in Europe, and its etiology is largely unknown, although it is very likely genetic and environmental factors contribute to this malformation. Orofacial development is a complex process involving many genes and signaling pathways. Mutations in the gene for the interferon regulatory factor 6 (IRF6) cause a hereditary dominant malformation syndrome including CL/P, and polymorphisms are associated with non-syndromic CL/P (MIM 119530). Five SNPs at the locus with high heterozygosity in Caucasian populations were chosen for the present research due to their very strong association with CL/P. A case-parent trio study was performed using 292 samples from Mexico. Association with the rs1319435-C/C genotype (P = 0.02) was found in patients (73) as compared to pseudocontrols (219), while the genotype rs1319435-T/C was related with protection (P = 0.041) in the triad design. Significant over-transmission of the G allele for marker rs2235375 (P = 0.049) was found. Only the TACGT haplotype was diminished in the affected child, either in single (P = 0.0208) or double (P = 0.0208) dose. The pairwise analysis showed rs2235543 and rs2235371 were in strong linkage disequilibrium. These results point to a substantial contribution of IRF6 in the etiology of non-syndromic CL/P in a sample of the Mexican population.