Human leukocyte antigen Class II alleles associated with acral lentiginous melanoma in Mexican Mestizo patients: A case-control study

Background: Melanoma is an aggressive cutaneous cancer. Acral lentiginous melanoma is a melanoma subtype arising on palms, soles, and nail-units. The incidence, prevalence and prognosis differ among populations. The link between expression of major histocompatibility complex Class II alleles and melanoma progression is known. However, available studies report variable results regarding the association of melanoma with specific HLA Class II loci. Aims: The aim of the study was to determine HLA Class II allele frequencies in acral lentiginous melanoma patients and healthy Mexican Mestizo individuals. Methods: Eighteen patients with acral lentiginous melanoma and 99 healthy controls were recruited. HLA Class II typing was performed based on the sequence-specific oligonucleotide method. Results: Three alleles were associated with increased susceptibility to develop acral lentiginous melanoma, namely: HLA-DRB1*13:01; pC = 0.02, odds ratio = 6.1, IC95% = 1.4–25.5, HLA-DQA1*01:03; pC = 0.001, odds ratio = 9.3, IC95% = 2.7–31.3 and HLA-DQB1*02:02; pC = 0.01, odds ratio = 3.7, IC95% = 1.4–10.3. Limitations: The small sample size was a major limitation, although it included all acral lentiginous melanoma patients seen at the dermatology department of Dr. Manuel Gea González General Hospital during the study period. Conclusion: HLA-DRB1*13:01, HLA-DQB1*02:02 and HLA-DQA*01:03 alleles are associated with increased susceptibility to develop acral lentiginous melanoma in Mexican Mestizo patients.

Risk Factors for Secondary Glaucoma in Patients with Vogt-Koyanagi-Harada Disease

Background: To identify the prevalence and risk factors for secondary glaucoma among Mexican-mestizo patients with Vogt-Koyanagi-Harada Disease (VKH). A retrospective cohort study was conducted to identify the risk factors for developing secondary glaucoma based on demographic, clinical, and epidemiological variables of VKH Mexican-mestizo patients. Risk estimates were calculated using a Cox proportional hazards regression model. Main text: One hundred eyes of 50 patients, 44 (88%) women and 6 men (12%) with a median age of 35.5 years (IQR 29 – 46), and a median follow-up time of 72 months (IQR 13.7 – 126.7) were included for analysis. The prevalence of glaucoma was 20%, with angle-closure glaucoma accounting for 70% of all cases. Significant clinical risk factors for glaucoma development were a chronic recurrent stage at presentation (RR 2.88 95% CI 1.11 – 12.63, p=0.037), more than two episodes of recurrent anterior uveitis (RR 8.52 95% CI 2.02 – 35.92, p<0.001), angle-closure disease (ACD, RR 7.08 95% CI 2.44 – 20.48, p<0.001), iris bombé (RR 5.0 95% CI 2.10 – 11.90, p<0.001), and peripapillary atrophy (RR 3.56 95% CI 1.43 – 8.85, p<0.001). Exposure to prednisone for more than 24 months (RR 9.33 95% CI 2.21 – 39.28, p<0.001) or topical corticosteroid drops for more than 12 months (RR 3.88 95% CI 1.31 – 11.46, p=0.007) were associated with an increased likelihood for secondary glaucoma development. Conclusions: Glaucoma is a frequent complication in patients with VKH, often attributed to mixed pathogenic mechanisms. Chronic disease at presentation, recurrent inflammation, angle-closure mechanisms, iris bombé, and peripapillary atrophy represent clinically significant risk factors for secondary glaucoma development. Prompt and aggressive steroid-spearing immunosuppressive therapy for reaching adequate control of inflammation may lower the risk of glaucoma in VKH patients.

Prevalence of protective haplotypes of the SLCO1B1 gene for statin transport in Mexican populations

Aim: To evaluate the genetic distribution of the rs4149056 and rs2306283 variants in the SLCO1B1 gene in Mexican Mestizo (admixed) and Native American groups. Materials & methods: We recruited 360 volunteers who were qPCR-genotyped with TaqMan probes. Results: Allele and genotype frequencies are reported. Among the expected rs4149056– rs2306283 haplotypes, T–A (42.35–58.47%) was the most prevalent which relates to the normal activity of the OATP1B1 transporter. This was followed by the T–G haplotype associated with further statin transport and cholesterol reduction (32.49–43.76%). Conclusion: Based on these SLCO1B1 gene variants, we confirmed that a minimum fraction of the Mexican study populations would be at risk from decreasing simvastatin transport and the development of statin-induced myopathy.

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.

ALG1-CDG Caused by Non-functional Alternative Splicing Involving a Novel Pathogenic Complex Allele

This study reports on a Mexican mestizo patient with a multi-systemic syndrome including neurological involvement and a type I serum transferrin profile. Clinical exome sequencing revealed complex alleles in ALG1, the encoding gene for the chitobiosyldiphosphodolichol beta-mannosyltransferase that participates in the formation of the dolichol-pyrophosphate-GlcNAc2Man5, a lipid-linked glycan intermediate during N-glycan synthesis. The identified complex alleles were NM_019109.5(ALG1): c.[208 + 16_208 + 19dup; 208 + 25G &gt; T] and NM_019109.5(ALG1): c.[208 + 16_208 + 19dup; 1312C &gt; T]. Although both alleles carried the benign variant c.208 + 16_208 + 19dup, one allele carried a known ALG1 pathogenic variant (c.1312C &gt; T), while the other carried a new uncharacterized variant (c.208 + 25G &gt; T) causing non-functional alternative splicing that, in conjunction with the benign variant, defines the pathogenic protein effect (p.N70S_S71ins9). The presence in the patient’s serum of the pathognomonic N-linked mannose-deprived tetrasaccharide marker for ALG1-CDG (Neu5Acα2,6Galβ1,4-GlcNAcβ1,4GlcNAc) further supported this diagnosis. This is the first report of an ALG1-CDG patient from Latin America.

Molecular Differences Between Squamous Cell Carcinoma and Adenocarcinoma Cervical Cancer Subtypes: Potential Prognostic Biomarkers

Purpose Cervical cancer (CC) remains a health problem. Persistent infection by high-risk papillomavirus (HR-HPV) is the main cause of this disease. The most frequently diagnosed histological types of CC are squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Clinically, the prognosis of both types is controversial. Our aim was to search for a molecular profile that distinguishes each histological subtype and predicts the prognosis of one or both subtypes would be of great benefit to these patients. Methods The transcriptome of CC patients from The Cancer Genome Atlas (TCGA) was analyzed using the DESeq2 package to obtain the differentially expressed genes between ADC and SCC. The differentially expressed genes obtained from the TCGA database were validated with an online, publicly available transcriptome dataset (GSE56303) containing data for a Mexican-Mestizo independent cohort. The global biological pathways involving differentially expressed genes between SSC and ADC were obtained by performing an analysis using the Webgestalt platform. In addition, associations of the differentially expressed genes with Overall Survival (OS) were assessed. Results The molecular profile of 70 altered transcripts between ADC and SCC patients from the TCGA cohort was determined. These transcripts were also deregulated in the Mexico-Mestizo cohort with the same Log2FoldChange values. The molecular pathways involved were IL-17, JAK/STAT and Ras signaling. Higher GABRB2 and TSPAN8 expression and lower TMEM40 expression were associated with better OS in the Mexican-Mestizo cohort. Conclusion We were able to detect molecular differences between the ADC and SCC subtypes of CC; however, further studies are required to define the appropriate prognostic biomarker for each histological type.

POS1074 CARDIOVASCULAR RISK FACTORS IN A MEXICAN MESTIZO PATIENTS WITH PSORIATIC ARTHRITIS

Background:Psoriatic Arthritis (PsA) is a chronic inflammatory arthropathy that affects 14%-30% of patients with skin and/or nail psoriasis. Patients with psoriatic arthritis (PsA) have a higher prevalence of traditional cardiovascular (CV) risk factors and an increased risk of developing cardiovascular diseases (1), such as acute myocardial infarction, cerebrovascular accident, peripheral vascular disease and heart failure. Despite the evidence patients with PsA are inadequately screened and undertreated for CV risk factors (CVRF), highlighting a gap in preventive medicine to adjust cardiovascular therapies(2).Objectives:The aim of the study is to determine the main CVRF in Mexican Mestizo patients with a diagnosis of PsA and to compare it with healthy controls. Additionally, to assess the impact of the diagnosis of PsA on the presence on these cardiovascular comorbidities.Methods:A cross-sectional, observational, and comparative study of ninety-six patients with PsA between 40-75 years who fulfilled CASPAR criteria 2006. Patients were matched by age and gender with non-PsA subjects. A medical history and physical exam were performed, also a blood sample was collected during the first visit. Chi square and Student´s t test were used for comparations between groups. A binary logistic regression was performed including the traditional CVRF (type 2 diabetes mellitus, hypertension, obesity, and active smoking), age and the diagnosis of PsA. A p value <0.05 was considered statistically significant.Results:There were 58 (60.4%) women in each group with a mean of 53 years. Patients with PsA showed a higher prevalence of hypertension (HTN) compared to healthy controls (35.4% vs 19.8%, respectively, p = 0.015). Additionally, there was a significant difference in the diagnosis of dyslipidemia (42.7% vs 22.9%, p = 0.003).We found no statistically difference between the two groups in type 2 diabetes mellitus, active smoking and, obesity (Table 1. below).Table 1.Comparison of cardiovascular risk factors between Psoriatic Arthritis and controls.PsA(n=96)Control(n=96)pAge, years ± SD53.19 ± 11.1353.34 ± 8.4NSWomen, n (%)58 (60.4)58 (60.4)NST2DM, n (%)21 (21.9)12 (12.5)NSHTN, n (%)34 (35.4)19 (19.8)0.015Active smoking, n (%)21 (21.9)20 (20.8)NSDyslipidemia, n (%)41 (42.7)22 (22.9)0.003Obesity, n (%)36 (37.5)25 (26.0)NSNS, no significative; SD, standard deviation; HTN, hypertension; T2DM, type2 diabetes mellitus.The binary logistic regression showed that the diagnosis of PsA (OR 2.235, 95% CI 1.141-4.375, p = 0.019) and active smoking (OR 2.429 95%, CI 1.137-5.186, p = 0.022) are independent risk factors for the presence of dyslipidemia.Conclusion:Patients with PsA have a higher prevalence of HTN and dyslipidemia. The diagnosis of PsA seems to be an independent factor for the presence of dyslipidemia. It is important for rheumatologists to identify those patients who could benefit from adjust antirheumatic and cardiovascular therapies due to their impact on morbidity and mortality.References:[1]Peluso R, Caso F, Tasso M, et al. Cardiovascular Risk Markers and Major Adverse Cardiovascular Events in Psoriatic Arthritis Patients. Rev Recent Clin Trials 2018;13(3):199-209. doi: 10.2174/1574887113666180314105511[2]Takeshita J, Grewal S, Langan SM, et al. Psoriasis and comorbid diseases: Implications for management. J Am Acad Dermatol 2017;76(3):393-403. doi: 10.1016/j.jaad.2016.07.065Disclosure of Interests:None declared.

Correlation between Chest X-Ray Severity in COVID-19 and Age in Mexican-Mestizo Patients: An Observational Cross-Sectional Study

Introduction. Chest X-ray (CXR) is used for the initial triage of patients with suspected COVID-19. Studies of CXR scoring in the European population found a higher score in males than in females and significantly correlated with age. Because there have not been studies in the Mexican-mestizo community, we aimed to compare the differences in CXR scores between males and females and their correlation with age after controlling comorbidities like diabetes and hypertension. Materials and Methods. A retrospective study of 1000 CXR of Mexican-mestizo patients with SARS-CoV-2 infection, confirmed by RT-PCR. Significant differences between age, age groups, symptoms, comorbidities, and CXR scores between males and females used the Mann–Whitney U , Chi-square tests ( χ 2 ), and Kruskal–Wallis tests. The relationship between the total CXR score and age was measured with the Spearman rank correlation coefficient (Rs); partial correlation analysis controlled the effect of symptoms, risk factors, and comorbidities. Results. The total CXR score did not show a difference between males and females grouped by age. There was a positive, low correlation between the total CXR score and age in males, Rs = 0.260 , p < 0.001 ( N = 616 ), and in females, Rs = 0.170 , p = 0.001 ( N = 384 ). Age only explained a <9% variance of CXR severity. Rs decreased its magnitude (from Rs = 0.152 to Rs = 0.046 ) and lost its significance (change in p value from p < 0.001 to p = 0.145 ) after controlling the effect of hypertension. Conclusions. There is no significant difference in CXR score between males and females in the Mexican-mestizo population grouped by age. Hypertension cancels the significance of CXR severity with age pointing to its role in the pathophysiology of COVID-19. Further research using stratified groups by age and gender in other populations needs to be published.