Role of Major Histocompatibility Complex Genes in the Susceptibility and Protection of Primary Open Angle Glaucoma and Primary Congenital Glaucoma

Introduction: Glaucoma is a prevalent disease seen in the Ophthalmology department that includes a group of neurodegenerative eye pathologies associated with total loss of vision. It is known for its clinical diversity and secondary to this, it is assumed that multiple genes play a role in its pathogenesis. Among these, those that regulate the immune response which includes the HLA genes are of particular interest because they have been associated with a subgroup of glaucoma patients known as Primary Open Glaucoma. Methods: In this study, we studied 3 different groups of patients with glaucoma in whom HLA alleles were determined by sequence-specific primers (SSP) technique. Results: An association of HLA-DRB1*16 was found with the susceptibility to develop Primary Congenital Glaucoma. In addition, HLA-DRB1*14 was associated with glaucoma without angular dysgenesis, and HLA-DRB1*03 to glaucoma with iridocorneal dysgenesis. Conclusion: In conclusion, the data obtained allow us to suggest that glaucoma is a clinical and genetically heterogeneous disease in which one of the subgroups has an autoimmune mechanism in which the Mexican mestizo population shows genetic susceptibility and it differs from POAG with angular dysgenesis and POAG without dysgenesis.

Demographic Profile and Clinical Course of Fuchs Endothelial Corneal Dystrophy in Mexican Patients.

Purpose To describe the demographic characteristics and clinical course of Fuchs endothelial corneal dystrophy (FECD) in a Mexican-mestizo population. Methods A retrospective observational and longitudinal study was performed in consecutive patients with the clinical diagnosis of Fuchs endothelial corneal dystrophy seen at our institution. Initial and last follow-up best corrected visual acuity, slit-lamp findings, and specular microscopy endothelial morphometric parameters were analyzed. Results One hundred and two eyes belonging to 51 patients were included in the analysis. Median age at the time of diagnosis was 69 years (range, 25–87 years) with a female-to-male ratio of 3.3:1. Visual loss (59.8%) and fluctuating matutine vision (7.8%) were the most common complaints at presentation. Regarding FECD staging, 65 (63.7%) were classified as stage-I FECD, 21 (20.6%) stage-II, and 15 (14.7%) as stage-III. A high percentage of eyes (44%) presented visual impairment (≤ 20/40) at presentation, and the presence of isolated corneal guttata was the most common stage of presentation (64%) at slit-lamp examination. Fifty-nine (57.8%) eyes did not require any medical or surgical management, and 17% of the evaluated eyes finally required a corneal transplantation, being penetrating keratoplasty with 8 (44.4%) eyes the most frequent technique performed. Conclusion Demographical characteristics of Fuchs dystrophy regarding age at presentation, gender distribution, and clinical stage at the time of diagnosis did not differ significantly from other international reports. Almost 20% of these patients will require keratoplasty during the disease, emphasizing the need for safer and more reproducible keratoplasty techniques.

Polymorphisms in Processing and Antigen Presentation-Related Genes and Their Association with Host Susceptibility to Influenza A/H1N1 2009 Pandemic in a Mexican Mestizo Population

(1) Background: The influenza A/H1N1 pdm09 virus rapidly spread throughout the world. Despite the inflammatory and virus-degradation pathways described in the pathogenesis of influenza A virus (IAV) infection, little is known about the role of the single nucleotide polymorphisms (SNPs) in the genes involved in the processing and antigenic presentation-related mechanisms. (2) Methods: In this case-control study, we evaluated 17 SNPs in five genes (TAP1, TAP2, TAPBP, PSMB8, and PSMB9). One hundred and twenty-eight patients with influenza A/H1N1 infection (INF-P) and 111 healthy contacts (HC) were included; all of them are Mexican mestizo. (3) Results: In allele and genotype comparison, the rs241433/C allele (TAP2), as well as AG haplotype (rs3763365 and rs4148882), are associated with reduced risk for influenza A/H1N1 infection (p < 0.05). On the other hand, the rs2071888G allele (TAPBP) and GG haplotype (rs3763365 and rs9276810) are associated with a higher risk for influenza A/H1N1 infection. In addition, after adjustment for covariates, the association to a reduced risk for influenza A/H1N1 infection remains with rs241433/C allele (p < 0.0001, OR = 0.24, 95% CI = 0.13–0.43), and the association with TAPBP is also maintained with the G allele (p = 0.0095, OR = 1.89, 95% CI = 1.17–3.06) and GG genotype models (p < 0.05, OR = 2.18, 95% CI = 1.27–3.74). (4) Conclusion: The rs241433/C allele and AC genotype (TAP2) and the AG haplotype are associated with a reduced risk for influenza A/H1N1 infection. In addition, the rs2071888/G allele and GG genotype (TAPBP) and the GG haplotype are associated with a higher risk for developing influenza A/H1N1 infection in a Mexican mestizo population.

Pharmacogenetic Evaluation of Metformin and Sulphonylurea Response in Mexican Mestizos with Type 2 Diabetes

Background: In Mexico, approximately 25% of patients with type 2 diabetes (T2D) have adequate glycemic control. Polymorphisms in pharmacogenetic genes have been shown to have clinical consequences resulting in drug toxicity or therapeutic inefficacy. Objective: The study aimed to evaluate the impact of variants in genes known to be involved in response to oral hypoglycemic drugs, such as CYP2C9, OCT, MATE, ABCA1 and C11orf65, in the Mexican Mestizo population of T2D patients. Methods: In this study, 265 patients with T2D were enrolled from the Hospital Juárez de México, Mexico City. Genotyping was performed by TaqMan® assays. SNP-SNP interactions were analyzed using the multifactor dimensionality reduction (MDR) method. Results: Carriers of the del allele of rs72552763 could achieve better glycemic control than noncarriers. There was a significant difference in plasma glucose and HbA1c levels among rs622342 genotypes. The results suggested an SNP-SNP interaction between rs72552763 and rs622342 OCT1 and rs12943590 MATE2. Conclusion: The interaction between rs72552763 and rs622342 in OCT1, and rs12943590 in MATE2 suggested an important role of these polymorphisms in metformin response in T2D Mexican Mestizo population.

Single Nucleotide and Copy-Number Variants in IL4 and IL13 Are Not Associated with Asthma Susceptibility or Inflammatory Markers: A Case-Control Study in a Mexican-Mestizo Population

Background: Asthma is a complex and chronic inflammatory airway disease. Asthma’s etiology is unknown; however, genetic and environmental factors could affect disease susceptibility. We designed a case-control study aimed to evaluate the role of single-nucleotide polymorphisms (SNP), and copy-number variants (CNV) in the IL4 and IL13 genes in asthma susceptibility and their participation in plasma cytokine levels depending on genotypes Methods: We include 486 subjects, divided into asthma patients (AP, n = 141) and clinically healthy subjects (CHS, n = 345). We genotyped three SNP, two in the IL4 and two in the IL13 gene; also, two CNVs in IL4. The IL-4, IL-13 and IgE plasma levels were quantified. Results: Biomass-burning smoke exposure was higher in the AP group compared to CHS (47.5% vs. 20.9%; p < 0.01, OR = 3.4). No statistical differences were found in the genetic association analysis. In both CNV, we only found the common allele. For the analysis of IL-4, IL-13, and IgE measures stratified by genotypes, no significant association or correlation was found. Conclusion: In the Mexican-mestizo population, SNPs neither CNVs in IL4 nor IL13 are associated with asthma susceptibility or involved serum cytokine levels. Biomass-burning smoke is a risk factor in asthma susceptibility.