Association between the TAP1 gene polymorphisms and recurrent respiratory papillomatosis in patients from Western Mexico: A pilot study.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a respiratory tract disease that affects children and adults and is characterized by the recurrent proliferation of multiple papillomas. The etiologic agent is the human papillomavirus, mainly genotypes 6 and 11. Furthermore, polymorphisms in TAP1 appear to influence the selection of antigenic peptides and the transport process to the rough endoplasmic reticulum, for their subsequent presentation to T lymphocytes, an essential process against viral diseases and tumor processes. Previous studies have shown that individuals with those polymorphisms are susceptible to immune, infectious, and tumor-related diseases. The present study aimed to determine the association between the TAP1 rs1057141 (c.1177A>G) and rs1135216 (c.2090A>G) single nucleotide polymorphisms (SNPs) and RRP. METHODS: A case-control study was carried out on a group of 70 individuals (35 controls and 35 patients). RRP diagnosis, HPV genotyping, and viral load were determined through histology and PCR. SNPs rs1057141 and rs1135216 were identified through allelic discrimination, using real-time PCR. The haplotypic analyses were performed using the Arlequin 3.5 program. RESULTS: HPV-6 and HPV-11 were the genotypes found in the samples. In the polymorphism analysis, rs1057141 showed no significant differences (p = 0.049, CI = 0.994-7.331). In contrast, a significant difference was found in rs1135216 (p = 0.039, OR = 2.4) in the allelic analysis, as well as in the dominant (p = 0.027, OR = 3.06), codominant (p = 0.033, OR = 3.06), and additive model (p = 0.043, OR = 2.505) in subjects with the G allele. CONCLUSION: The G allele in rs1135216 was associated with a genetic risk of susceptibility for RRP in a population in Western Mexico.

Detection of monoclonal B cells in general population from two different regions of Mexico.

To estimate the frequency of monoclonal B cells in Mexican general population from two different regions of Mexico. Monoclonal B cells were detected by rearrangements of the immunoglobulin heavy chains (IGH) in 288 individuals: 188 from a metropolitan area and 100 from a rural area. After DNA extraction from peripheral blood by the CTAB/DTAB method, multiplex PCR was used to amplify the IGH rearrangements, followed by capillary electrophoresis. In together, 9.4% of the studied individuals showed monoclonal B cells. This prevalence is significantly higher to those previously described for other populations, but similar to a report in the Spanish population. Among people from the metropolitan area, 12.8% exhibited monoclonal B cells in comparison with 3% of people from the rural area. All individuals showing monoclonal B cells were elder than 40 years. Higher frequency of incomplete monoclonal rearrangements was observed. Individuals from urban areas show significantly increased frequencies of monoclonal B cells regarding the people from the rural area. It is reasonable to believe that the environmental factor could have a greater impact on the development of monoclonality than the genetic component.

Effect of APOB gene polymorphisms on body mass index, blood pressure, and total cholesterol levels: A cross-sectional study in Mexican population.

APOB gene polymorphisms are considered risk factors for the development of dyslipidemia, hypertension, and cardiovascular disease (CVD) in several populations. In Mexico, these pathologies are frequent and studies regarding this gene are scarce. The aim of this cross-sectional study was to determined genotype, allele, and haplotype frequencies of APOB polymorphisms and performed analyses of association among the biochemical, hemodynamic, anthropometrical, and genetic variables. Blood samples were taken from 361 subjects from unselected Mexican population for biochemical analysis and for deoxyribonucleic acid extraction; besides blood pressure and body mass index (BMI) were measured. APOB polymorphisms rs934197, rs533617, rs693, and rs1042031 were genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism; whereas, rs17240441 and c.66_67insCTGCTG were genotyped by PCR followed by electrophoresis. Genotype and allele frequencies were obtained by simple counting and deviations from Hardy-Weinberg equilibrium (HWE) were calculated by chi-square test. The effect of the polymorphisms on the quantitative variables was determined using analysis of variance, Student's t test, Pearson's and Spearman's correlations and multiple linear regression models. All the polymorphisms were within HWE. Frequencies of mutated alleles were highly heterogeneous: rs934197-T 33.6%, rs17240441-D 39.3%, c.66_67insCTGCTG-I 3.9%, rs533617-G 0.9%, rs693-T 40.5%, and rs1042031-G 17.3%. Chronic degenerative diseases were frequent in the studied population: overweight-obesity 55.1%, dyslipidemia 45.8%, and hypertension 23.5%. The association analyses showed that despite adjustments for age and sex the mutated alleles rs934197-T, rs1042031G, c.66_67-insCTGCTG-I, and rs533617-G, were related to lower values of BMI, total cholesterol (TC), systolic blood pressure, and diastolic blood pressure, respectively. All polymorphisms analyzed except rs533517 and c.66_67insCTGCTG showed high frequencies of the mutated allele, making them useful for association studies. Our results revealed that, APOB gene polymorphisms could be contributing to the development of several chronic diseases, such as essential hypertension, dyslipidemias, obesity, among others. However, specific studies with each pathology are needed to know the possible implications of the polymorphisms.

Association of TAP1 1177A>G and 2090A>G gene polymorphisms with latent tuberculosis infections in sheltered populations, in the metropolitan area of Guadalajara, Mexico: a pilot study.

Latent tuberculosis infection (LTBI) is a condition that has no clinical signs and symptoms. LTBI patients are characterized by persistent immune responses to Mycobacterium tuberculosis, and approximately 5-10% of these infected individuals will develop active TB at some point in their lives. The antigen transporter associated with antigen processing (TAP1) is a protein involved in the transport of the antigen from the cytoplasm to the endoplasmic reticulum by means of the association with MHC class I molecules. It plays a fundamental role in the immune response, promoting the clearance of intracellular pathogens. Our pilot study aimed to determine the association between TAP1 gene 1177A>G (rs1057141) and 2090A>G (rs1135216) genetic polymorphisms with susceptibility to LTBI. In this case-control study, 153 individuals from shelters were analyzed (46 were LTBI-positive and 92 were controls). Genotyping of the rs11352216 (2090A>G) and rs1057141 (1177A>G) gene IDs was performed using the Applied Biosystems Step One Thermal Cycler Real-Time PCR allelic discrimination technology. The haplotypic analyses were performed with the Arlequin 3.5 program. Social assistance centers and shelters that serve vulnerable populations represent high-risk sites due to overcrowding and the impaired nutritional status of their residents. The G allele (OR=1.99, CI=1.109-3.587, p=0.021) and the GG genotype of rs11352216 (A>G) were associated with susceptibility to LTBI, according to the codominant genetic model (OR=8.32, CI=1.722-61.98, p=0.007). The rs1057141 (A>G) polymorphism was not associated with LTBI risk. The results suggest that carriers of the G allele of rs1135216 (A>G) are susceptible to LTBI.

LDLR Gene Mutation p.Asp360His and Familial Hypercholesterolemia in a Mexican Community.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by an increased LDL-cholesterol (LDLc) serum concentration and premature cardiovascular disease. Screening of small populations where at least one homozygous (HoFH) patient has been identified may be a proper approach for detecting FH patients. Previously, we reported an HoFH patient carrying the mutation p.Asp360His LDLR, who was born in the Mexican community El Triunfo (Quimixtlan, Puebla). AIM OF THE STUDY: To identify patients with familial hypercholesterolemia in the community El Triunfo and to describe their clinical and biochemical characteristics. METHODS: We studied 308 individuals by quantifying lipid levels and by DNA sequencing. RESULTS: Sixteen of 308 individuals presented an LDLc level >170 mg/dL and all of them turned out to be heterozygous for the LDLR p.Asp360His variant. Subsequently, 34 of their first-degree relatives (mainly siblings and parents) were genotyped rendering six additional HeFH patients, which resulted in 22 carriers of the mutated allele. The study of six LDLR polymorphisms in four unrelated individuals from the community (one HoFH and three HeFH) showed the same haplotype combination, suggesting a unique ancestral origin of the mutation. CONCLUSIONS: The community El Triunfo, has the highest worldwide frequency ever reported of HeFH, with 7.14% (22/308, equivalent to 1/14 inhabitants). Since the HeFH patients showed variable biochemical expression, we suggest looking for factors with the potential to modify the phenotype. Finally, we stress the importance of establishing accurate LDLc cut-off points applicable to Mexican population for the diagnosis of FH.