Miguel Ángel Reyes-López

Frequency of S and Z alleles for alpha-1-antitrypsin and tumor necrosis factor alpha 308 promoter polymorphism in northeastern Mexico

Diseases characterized by airway inflammation, excessive secretion, and obstruction affect a substantial proportion of the population. Studies for understanding the mechanisms underlying these processes are focused on the initiation and maintenance of inflammation. Polymorphisms on DNA sequence of response mediators such as alpha-1-antitrypsin (AAT) and tumor necrosis factor (TNF) alpha have the capacity to influence presentation of diseases, affecting protein amount and/or functionality, and can be analyzed as disease modulators. The purpose of this study was to analyze AAT S and Z alleles and -308G/A TNF-alpha polymorphism on the northeast Mexico mestizo population to compare the influence of these genes in several diseases. DNA samples from 103 volunteers (healthy group) were tested for modifier gene variants by polymerase chain reaction-RFLP as follows: AAT gene for S and Z alleles and TNF-alpha promoter -308G/A (TNF1/TNF2) alleles. Allele frequency for S and TNF2 alleles were 1.5 and 2.4%, respectively, whereas the Z allele was not detected. This study shows low frequencies of the AAT S and TNF2 alleles, and the Z allele was not found. Correlation studies in the future will allow to determine if these alleles have some influence in the clinical presentation of diverse diseases in this group of people.

Genetic Polymorphisms Associated to Folate Transport as Predictors of Increased Risk for Acute Lymphoblastic Leukemia in Mexican Children

Acute lymphoblastic leukemia (ALL) is a frequent neoplasia occurring in children. The most commonly used drug for the treatment of ALL is methotrexate (MTX), an anti-folate agent. Previous studies suggest that folate transporters play a role in ALL prognosis and that genetic polymorphism of genes encoding folate transporters may increase the risk of ALL. Therefore, the main goal of this study was to determine the associations among six genetic polymorphisms in four genes related with the folate transporter pathway to determine a relationship with the occurrence of ALL in Mexican children. A case-control study was performed in 73 ALL children and 133 healthy children from Northern and Northwestern Mexico. COL18A1 (rs2274808), SLC19A1 (rs2838956), ABCB1 (rs1045642 and rs1128503), and ABCC5 (rs9838667 and rs3792585). Polymorphisms were assayed through qPCR. Our results showed an increased ALL risk in children carrying CT genotype (OR = 2.55, CI 95% 1.11–5.83, p = 0.0001) and TT genotype (OR = 21.05, CI 95% 5.62–78.87, p < 0.0001) of COL18A1 rs2274808; in SLC19A1 rs2838956 AG carriers (OR = 44.69, CI 95% 10.42–191.63, p = 0.0001); in ABCB1 rs1045642 TT carriers (OR = 13.76, CI 95% 5.94–31.88, p = 0.0001); in ABCC5 rs9838667 AC carriers (OR = 2.61, CI 95% 1.05–6.48, p < 0.05); and in ABCC5 rs3792585 CC carriers (OR = 9.99, CI 95% 3.19–31.28, p = 0.004). Moreover, several combinations of genetic polymorphisms were found to be significantly associated with a risk for ALL. Finally, two combinations of ABCC5 polymorphisms resulted in protection from this neoplasia. In conclusion, certain genetic polymorphisms related to the folate transport pathway, particularly COL18A1 rs2274808, SLC19A1 rs2838956, ABCB1 rs1045642, and ABCC5 rs3792585, were associated with an increased risk for ALL in Mexican children.

The Tumor Necrosis Factor α (-308 A/G) Polymorphism Is Associated with Cystic Fibrosis in Mexican Patients

Environmental and genetic factors may modify or contribute to the phenotypic differences observed in multigenic and monogenic diseases, such as cystic fibrosis (CF). An analysis of modifier genes can be helpful for estimating patient prognosis and directing preventive care. The aim of this study is to determine the association between seven genetic variants of four modifier genes and CF by comparing their corresponding allelic and genotypic frequencies in CF patients (n = 81) and control subjects (n = 104). Genetic variants of MBL2 exon 1 (A, B, C and D), the IL-8 promoter (−251 A/T), the TNFα promoter (TNF1/TNF2), and SERPINA1 (PI*Z and PI*S) were tested in CF patients and control subjects from northeastern Mexico by PCR-RFLP. Results The TNF2 allele (P = 0.012, OR 3.43, 95% CI 1.25–9.38) was significantly associated with CF under the dominant and additive models but was not associated with CF under the recessive model. This association remained statistically significant after adjusting for multiple tests using the Bonferroni correction (P = 0.0482). The other tested variants and genotypes did not show any association with the disease. Conclusion An analysis of seven genetic variants of four modifier genes showed that one variant, the TNF2 allele, appears to be significantly associated with CF in Mexican patients.

Molecular detection of mixed infections with multiple dengue virus serotypes in suspected dengue samples in Tamaulipas, Mexico

This study aimed to detect dengue virus (DENV) serotypes in serum samples obtained in Matamoros Tamaulipas, Mexico, and to determine the concordance of conventional nested reverse transcriptase polymerase chain reaction (RT-PCR) and a serological test [enzyme-linked immunosorbent assay (ELISA NS1)]. Here, we detected mixed infections consisting of four serotypes of DENV. The most prevalent serotype was DENV-1, followed by DENV-4. This is the first report of DENV-4 in our region. Mixed infections were also detected in 21.5% of samples, and the predominant coinfection consisted of DENV-1 and DENV-2. Therefore, continuous epidemiological surveillance of DENV in this area is required to predict future forms of dengue heterologous infections and the effect of this on health care.

Prevalence, antimicrobial resistance and virulence genes in Escherichia coli isolated from retail meats in Tamaulipas, México.

OBJECTIVES The aim of this study was to determinate the prevalence of Escherichia coli and its resistance to antimicrobials and the presence of virulence genes in retail samples of beef and pork in several locations in Tamaulipas, Mexico. METHODS A total of 106 samples (54 beef and 52 pork) collected from August 2013 to March 2014 were analysed to detect E. coli isolates. The E. coli isolates were then analysed for detection of virulence factors and antimicrobial resistance genes. Antimicrobial susceptibility to 16 antimicrobial agents was also determined. RESULTS A total of 158 E. coli isolates were obtained, among which 3 (1.9%) harboured the virulence gene stx1, 28 (17.7%) harboured stx2 and 34 (21.5%) harboured hlyA. High phenotypic resistance was observed in almost all isolates, since 146 (92.4%) showed a multiresistant phenotype with resistance to cefalotin (92%), ampicillin (92%), cefotaxime (78%), nitrofurantoin (76%) and tetracycline (75%). The antimicrobial resistance genes tet(A) and tet(B) were detected in 56% of isolates, strA in 9.6%, aadA in 17% and aac(3)-IV in only 0.6% of strains. CONCLUSIONS Based on these results, it can be concluded that retail beef and pork meat may play a role in the spread of antimicrobial-resistant E. coli strains in this region.

Frequency of the L1014F Mutation in the Sodium Channel Gene, in Culex quinquefasciatus (Diptera: Culicidae) Populations From Rural and Urban Areas of Yucatan State, Mexico

Abstract Culex quinquefasciatus Say (Diptera: Culicidae) is a mosquito species that has attracted a lot of attention from a medical and veterinary point of view; however, little is known about the frequency of L1014F mutations that have been found in the sodium channel gene, with this being a target for DDT and pyrethroid insecticides. The distribution and frequency of the L1014F mutation in Cx. quinquefasciatus populations was determined in rural and urban areas of Yucatan, Mexico from January 2015 to March 2016. Nine hundred fifty adult females out of 17,727 immature states were collected and analyzed in all sites sampled (n = 10). Susceptible homozygotes were identified (L1014/L1014) in 12% (114/950), heterozygous individuals (F1014/L1014) in 34% (323/950), and mutated homozygotes (F1014/F1014) in 54% (513/950) during the dry and rainy seasons. In this work, study areas with a high frequency of L1014F mutation were identified. These findings may help guarantee a more effective and efficient use of the resources available for the control of this vector.

Analysis of interleukin-8, alpha1-antitrypsin, and tumor necrosis factor-alpha as biomarkers of breast cancer in women of northeastern Mexico.

18 Background: Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease and variations of protein values in plasma. Interleukin (IL)-8, alpha 1-antitrypsin (AAT) and tumor necrosis factor-alpha (TNF alpha) have been related to carcinogenesis in breast tissue. Whether polymorphisms of the genes and protein values also influence breast cancer risk is unclear. The objective was to analyze the levels and polymorphisms of biomarkers in breast cancer patients for diagnostic purposes. METHODS In this cases-controls study a total of 30 patients with breast cancer confirmed by histopathology and 21 healthy individuals were studied, both groups were of three generations born in the Northeast of Mexico. Two polymorphisms of the AAT gene (Alleles Z and S), a polymorphism of IL-8 (-251 A/T polymorphism of the IL-8 promoter), and the polymorphism of TNF-alpha [-308 G/A (TNF1/TNF2) polymorphism of the TNF-alpha promoter gene] were analyzed using PCR-RFLP. Additionally, the plasma protein values of the biomarkers were measured by ELISA. RESULTS The IL-8 (-251T) and TNF-alpha (-308G) polymorphisms were significantly associated with breast cancer. Odds ratios for women with one high-risk allele versus women homozygous for the low-risk allele were 4.06 for -308G TNF-alpha (95% confidence interval, 1.298-13.678; P = 0.006) and 2.44 for -251T IL-8 (95% confidence interval, 1.277-4.7; P = 0.003). Significant differences between protein values of patients and controls were observed (ATT U=63, Z=4.81, p (2) <0.0001; IL-8 U=112.5, Z=3.87 p (2) =0.0001; TNF-α U=135.5, Z=3.43, p (2) =0.0006), AAT and IL-8 were over-expressed in patients with breast cancer. The presence of the polymorphism does not influence the protein values (TNF rs=0.1203, IL-8 rs=0.2246), apparently. No association between presences of the polymorphism. CONCLUSIONS In this study, the presence of the IL-8 (-251T) and TNF-alpha (-308G) alleles may increase the risk of breast cancer in these Mexican women. Over-expression of IL-8 and AAT may directly correlate to the pathogenesis of breast cancer. Both biomarkers may be combined with other markers for presumptive diagnosis.