Mestizo Population Research Articles

Considerations about race and identity in the conformation of Latin America

This essay aims to carry out a brief analysis of the conformation of Latin America. Among the results, it has been visualized the evident role that, confessional clashes and political-economic disputes between the colonizing countries have had in the implantation of relationships based on forms of hierarchization, segregation and discrimination of the Amerindian, Afro-descendant, and mestizo populations, during the process of conquest and the subsequent independence. Especially considering the need on the maintenance of the domination of the colonial powers and the subsequent colonial caste system in the periods of “independent” life. At the same time that it is urged, given the contemporary conditions, for the discussion and deep reflection of issues such as alter subjectivities and Otherness. In this way, an exposition of the subject is carried out, beginning with the repercussions and characteristics of the colonial era, followed by a review of the particularities and effects that occurred in the post-Independence times, to continue with an analysis of some current debates around subjectivities and identities, ending with a discussion on the conclusions of the process.

Echocardiographic manifestations during the first 3 months after an episode of COVID-19 and their relationship with disease severity and persistence of symptoms

BackgroundCardiovascular manifestations in patients with COVID-19 are associated with dire outcomes. Long COVID syndrome is the persistence of symptoms after acute disease and is found in up to 40% of subjects. There is little information regarding subacute echocardiographic manifestations after COVID-19, and no study has included a Mexican mestizo population. MethodsThis cross-sectional study included subjects older than 18 with an episode of COVID-19 in the last 3 months. Those with previously known cardiovascular disease were excluded. The patient´s medical history and COVID-19 information were obtained from clinical charts. We performed a transthoracic echocardiogram in every subject and determined left ventricular (LV) index mass, LV ejection fraction (LVEF), left ventricular global longitudinal strain (LV GLS), right ventricular (RV) GLS, and tricuspid annular plane systolic excursion (TAPSE). A descriptive and comparative analysis was performed based on symptom severity and persistence. ResultsOne hundred subjects were included; 63% were classified with mild and 37% with moderate to severe COVID-19. The median of LVEF was 60% (55–60), LV GLS and RV GLS was impaired in 34% and 74% of patients, respectively. Patients with moderate to severe disease had significantly lower LVEF (Mean Difference: -3.3), TAPSE (mean difference: -1.8), and higher (worse) LV GLS (Mean Difference: 2.5) and RV GLS (mean difference: 2.9). Persistent symptoms were associated with lower TAPSE and higher RVGLS. ConclusionsPatients who recover from COVID-19 have a high prevalence of subtle RV and LV dysfunction using GLS analysis. A moderate to severe episode was associated with worse RV and LV function measured by RV GLS, TAPSE, and LV GLS. Subjects with persistent symptoms had worse RVGLS and TAPSE.

Variants in the Control Region of Mitochondrial Genome Associated with type 2 Diabetes in a Cohort of Mexican Mestizos

According to the International Diabetes Federation, Mexico is seventh place in the prevalence of type 2 diabetes (T2D) worldwide. Mitochondrial DNA variant association studies in multifactorial diseases like T2D are scarce in Mexican populations. The objective of this study was to analyze the association between 18 variants in the mtDNA control region and T2D and related metabolic traits in a Mexican mestizo population from Mexico City. This study included 1001 participants divided into 477 cases with T2D and 524 healthy controls aged between 42 and 62 years and 18 mtDNA variants with frequencies >15%. Association analyses matched by age and sex showed differences in the distribution between cases and controls for variants m.315_316insC (p = 1.18 × 10-6), m.489T>C (p = 0.009), m.16362T>C (p = 0.001), and m.16519T>C (p = 0.004). The associations between T2D and variants m.315_316ins (OR = 6.13, CI = 3.42-10.97, p = 1.97 × 10-6), m.489T>C (OR = 1.45, CI = 1.00-2.11, p = 0.006), m.16362T>C (OR = 2.17, CI = 1.57-3.00, p = 0.001), and m.16519T>C (OR = 1.69, CI = 1.23-2.33, p = 0.006) were significant after performing logistic regression models adjusted for age, sex, and diastolic blood pressure. Metabolic traits in the control group through linear regressions, adjusted for age, sex and BMI, and corrected for multiple comparisons showed nominal association between glucose and variants m.263A>G (p <0.050), m.16183A>C (p <0.010), m.16189T>C (p <0.020), and m.16223C>T (p <0.024); triglycerides, and cholesterol and variant m.309_310insC (p <0.010 and p <0.050 respectively); urea, and creatinine, and variant m.315_316insC (p <0.007, and p <0.004 respectively); diastolic blood pressure and variants m.235A>G (p <0.016), m.263A>G (p <0.013), m.315_316insC (p <0.043), and m.16111C>T (p <0.022). These results demonstrate a strong association between variant m.315_316insC and T2D and a nominal association with T2D traits.

Frequent copy number variants in a cohort of Mexican-Mestizo individuals

BackgroundThe human genome presents variation at distinct levels, copy number variants (CNVs) are DNA segments of variable lengths that range from several base pairs to megabases and are present at a variable number of copies in human genomes. Common CNVs have no apparent influence on the phenotype; however, some rare CNVs have been associated with phenotypic traits, depending on their size and gene content. CNVs are detected by microarrays of different densities and are generally visualized, and their frequencies analysed using the HapMap as default reference population. Nevertheless, this default reference is inadequate when the samples analysed are from people from Mexico, since population with a Hispanic genetic background are minimally represented. In this work, we describe the variation in the frequencies of four common CNVs in Mexican-Mestizo individuals.ResultsIn a cohort of 147 unrelated Mexican-Mestizo individuals, we found that the common CNVs 2p11.2 (99.6%), 8p11.22 (54.5%), 14q32.33 (100%), and 15q11.2 (71.1%) appeared with unexpectedly high frequencies when contrasted with the HapMap reference (ChAS). Yet, while when comparing to an ethnically related reference population, these differences were significantly reduced or even disappeared.ConclusionThe findings in this work contribute to (1) a better description of the CNVs characteristics of the Mexican Mestizo population and enhance the knowledge of genome variation in different ethnic groups. (2) emphasize the importance of contrasting CNVs identified in studied individuals against a reference group that—as best as possible—share the same ethnicity while keeping this relevant information in mind when conducting CNV studies at the population or clinical level.

Second Neoplasms in Diffuse Large B-Cell Lymphoma: The Role of Race

Aim: Patients with diffuse large B-cell lymphoma, (DLBCL) have an increased risk to develop a second neoplasm (SN). Multiple factors have been considered at risk: age, familial history, smoking, use of alkylating agents, or etoposide at increased doses, and especially radiotherapy. Moreover, most of the studies have been performed in USA and Europe countries, with a preponderance of white population. The aim of the study is analyze a large number of patients with DLBCL in a search to define the presence of SN in a Mestizo population. Patients and Methods: Electronic files of patients with pathological confirmed diagnosis of DLBCL, treated in our hospital between August 1988 to December 2020; age> 18 years age treated, with combined chemotherapy that were in complete response for at least 3 years. Probably factors associated were analyzed. Median follow-up were 22.4 (range 3.1 to 31.8) years. Results: A total of 9316 patients were evaluated, only 16 cases (0.16%) developed SN. Neither of previous mentioned risks factors: age, gender, smoking doses of chemotherapeutic drugs, alkylating agents, use of radiotherapy, advance stage, elevated International Prognostic index, history of cancer, not were associated to the development of a SN, only race were different, 98 % of our patients were mestizo race. Until now race has not been considered as a factor to be associated with the development of a SN. Conclusion: The unique differences in large number of cases and longer follow-up, was that the presence of an non-white populations, thus it is appear that in an Mestizo population race could have any protective possibility.

Sociocultural drivers of mycological knowledge: insights from Wixarika and Mestizo groups in western Mexico

BackgroundTraditional mycological knowledge (TMK) is complex, not distributed equally among the entire population, and constantly adapting to current social situations. There are sociocultural factors that could influence the fact that some people retain a greater wealth of knowledge, for instance, cultural affiliation, migration, occupation, level of schooling, and person's age. MethodsWe analyze the distribution of the TMK based on sociocultural variables and 12 indicators to quantify the TMK based on a literature review. We chose two sites where there was a Wixarika and Mestizo population with records of use and consumption of wild mushrooms. In each site, 150 semi-structured interviews were conducted. The format of the semi-structured interviews was made up of sociocultural questions plus 12 questions corresponding to each of the indicators. With the data obtained, we performed linear regression tests and principal components analysis (PCA); furthermore, the significance of the groupings obtained by PCA was tested with a discriminant function analysis.ResultsWe find that TMK was determined by the cultural group to which a person belongs. Contrary to what was expected, age and formal schooling did not influence people's level of knowledge. Likewise, migration and occupation were not determining factors either, although in some specific cases they did influence the differences in knowledge about mushrooms between people. The indicators that most helped to differentiate between the Wixarika people, and the Mestizos were knowledge of the nutritional contribution, propagation methods, and knowledge about toxic mushrooms.ConclusionsIn general, sociocultural differences did not affect the transmission of the TMK due to the valorization of this knowledge among the young generations and the maintenance of the use of wild resources. Specifically, the Wixaritari had and preserved a greater TMK thanks to their pride in their cultural identity, which had allowed them to adapt to modernity while preserving their traditions and knowledge. On the other hand, the Mestizos increasingly disused wild resources due to urbanization. The indicators proposed here provided a good tool to quantify TMK; however, to replicate the study in other sites it is necessary to adapt the indicators to the context of the place.

The HLA-DRB1*07 Allele Is Associated with Interstitial Lung Abnormalities (ILA) and Subpleural Location in a Mexican Mestizo Population.

Interstitial lung abnormalities (ILA) are defined as the presence of different patterns of increased lung density, including ground glass attenuation and reticular opacities on chest high-resolution computed tomography (HRCT). In this study, we included 90 subjects with ILA and 189 healthy controls (HC) from our Aging Lung Program. We found that subjects with ILA are older, have a significant smoking history, and have worse pulmonary function than HC (p < 0.05). When we evaluated the allele frequencies of the human leukocyte antigen (HLA) system, we found that HLA-DRB1*07 was associated with a higher risk for ILA (p < 0.05, OR = 1.95, 95% CI = 1.06-3.57). When we compared subjects with subpleural ILA vs. HC, the association with HLA-DRB1*07 became stronger than the whole ILA group (p < 0.05, OR = 2.29, 95% CI = 1.24-4.25). Furthermore, subjects with subpleural ILA and central ILA display differences in allele frequencies with HLA-DRB1*14 (3.33% vs. 13.33%, p < 0.05) and *15 (3.33% vs. 20%, p < 0.05). Our findings indicate that the HLA-DRB1*07 allele contributes to the risk of ILA, especially those of subpleural locations.

ALL-350 Characterization of Acute Lymphoblastic Leukemia in the Pediatric Mexican Mestizo Population

Acute lymphoblastic leukemia (ALL) is the most common neoplasm of lymphoid progenitor cells in pediatric populations. ALL cases can be broadly classified as B-cell or T-cell. B-cell ALL (B-ALL) has many genetic subtypes characterized by major chromosomal alterations. Flow cytometry and biomarkers identification provide information about the subtype of ALL and can be correlated with the patient's prognosis. Based on reactivity with antigens present on the surface or in the cytoplasm of leukemia cells, B-ALL can be divided into 4 subtypes according to its stage of differentiation: pro-B, common B, pre-B, and immature B subtypes. This study aims to establish the association of the molecular biomarkers TCF3-PBX1 t(1;19), rearrangement of MLL t(4;11), BCR-ABL1 t(9;22), and ETV6-RUNX1 t(12;21) with ALL subtypes according to its stage of differentiation. The study includes a retrospective analysis of laboratory data results from the Mexican mestizo pediatric population diagnosed with ALL during a 3-year period (2018-2021), referred to Mendel laboratories from different health institutions. Ninety ALL cases, age range 0-17 years, were classified by immunophenotype and tested by PCR for the biomarkers TCF3-PBX1, rearrangement of MLL, BCR-ABL1, and ETV6-RUNX1. The biomarkers tested were expected to be present in most of the cases (>50%) regardless of the differentiated ALL subtype. B-cell ALL represented 92.2% of the cases (83); the prevailing subtype was pre-B with 51.1% of all cases. The biomarkers TCF3-PBX1, rearrangement of MLL, BCR-ABL1, and ETV6-RUNX1 were present in at least one case in the subtype pro-B. ETV6-RUNX1 was identified as the only marker in common B-ALL. Seventy-one percent of the cases showed no presence of the 4 biomarkers tested and correspond to quadruple negative cases. The biomarkers TCF3-PBX1, rearrangement of MLL, BCR-ABL1, and ETV6-RUNX1 are decisive in establishing the prognosis of patients with any of the ALL-B subtypes and enable the definition of a stratified treatment. The absence of these markers prevails in the study population, so it is essential to include other recently described mutations in laboratory determinations. Laboratorios MENDEL, Morelia Michoacán. México.

Increased Carotid Intima-Media Thickness in Asymptomatic Individuals Is Associated with the PCSK9 (rs2149041) Gene Polymorphism in the Mexican Mestizo Population: Results of the GEA Cohort.

The increase in carotid intima-media thickness (CIMT) and coronary artery calcification (CAC) are features of subclinical atherosclerosis that might be determined by the genetic background of patients. Among the multiple risk factors, the proprotein convertase subtilisin kexin type 9 (PCSK9) has a great impact on atheroma development. Then, we focused on the potential association of the PCSK9 gene polymorphism (rs2149041) with the risk of an increased CIMT. We included 881 unrelated, asymptomatic individuals (732 normal CIMT and 149 increased CIMT) who lacked coronary calcification (CAC score = 0). Under the recessive inheritance model and adjusted by several cardiovascular risk factors, the rs2149041 polymorphism, determined by TaqMan genotyping assay, was associated with a high risk of increased CIMT (OR = 2.10, 95% IC = 1.26–3.47, P recessive = 0.004). Our results suggest that the rs2149041 polymorphism could be a risk marker for increased CIMT in asymptomatic individuals without coronary artery disease determined by the absence of a CAC score.

Anatomical and Clinical Factors Associated With Valvulopathy and Aortopathy in Mexican Patients With Bicuspid Aortic Valves

The bicuspid aortic valve (BAV) is associated with significant aortic valve dysfunction. We aimed to study Mexican patients with BAV to assess phenotypic expressions of BAV, and associations of valvulopathy and aortopathy and their predictors. A cross-sectional, retrospective study was designed. The patients were divided according to (1) normally or minimally dysfunctional BAV, (2) predominant aortic regurgitation (AR), and (3) predominant aortic stenosis (AS). A total of 189 patients were included with a high prevalence of males (68%). The overall median age was 42 (23 to 52) years. The distribution of fused BAV phenotypes was right-left fusion (77%), right noncoronary fusion (17%) and left noncoronary fusion (6%). AS-predominant group was the oldest with a high prevalence of hypertension, type 2 diabetes mellitus (T2DM), and raphe. In multivariable analysis T2DM (odds ratio [OR] 10.5 [95% confidence interval (CI) 2.1 to 52], p <0.01) and presence of raphe (OR 2.58 [95% CI 1.02 to 6.52], p=0.04) were independently associated with AS. The AR-predominant group was composed mostly of males with significantly fewer cardiovascular risk factors. Male gender (OR 2.84 [95%CI 121 to 6.68], p=0.01) and aortic dilatation (OR 3.58 [95% CI 1.73 to 7.39], p <0.01) were associated with AR-predominance in multivariable analysis. Aortic dilatation was associated with age (OR 1.03 [95% CI 1.008 to 1.05], p <0.01) and AR (OR 4.31 [95% CI 2.05 to 9.06], p <0.01). Independent factors associated with the root phenotype were male gender (OR 12.4 [95% CI 1.6 to 95], p <0.01) and AR (OR 5.25 [95% CI 2.18 to 12.6], p <0.01).In conclusion, in a mestizo population, the distribution of BAV-fused phenotypes was similar to European and North American populations, the presence of raphe and T2DM were independently associated with AS-predominance, and male gender and aortic dilatation were independently associated with AR-predominance.

P8.018: Human Leukocyte Antigen Tissue Typing in a Guatemalan Transplant Center

Introduction: The Kidney Transplant Program at the Hospital General San Juan de Dios (HGSJDD) began in 1992, to date more than 700 transplants have been performed, of these only 15% were from cadaveric sources. The Histocompatibility and Immunogenetics Laboratory, was funded in 2012 as part of the Nephrology and Transplant Department, back in that year tissue typing was performed by Complement Dependent Cytotoxicity (CDC), spanning the last decade the laboratory implemented other tissue typing techniques and anti-HLA antibody analysis, which represented an important advance for the transplant program and the country of Guatemala, since it is the only public laboratory that performs molecular biology and Luminex techniques. Herein we present the preliminary findings of HLA-A, B, DRβ1 and DQβ1 tissue typing using an SSOP-PCR based technique in 127 patients at the HGSJDD Kidney Transplant Program. Methods: 127 patients from the HGSJDD Kidney Transplant Program were recruited from January 2018 to December 2020, unrelated to each other, without a known diagnosis of diseases mediated by the major histocompatibility complex, and 100% self-identified as mestizos, all agreed to participate; the research was approved by the ethics and research committee of the HGSJDD and was conducted in accordance with the Helsinki Declaration principles. HLA genotyping was performed using a PCR-SSOP Luminex® method. HLA-A~B~DRβ1~DQβ1 allelic and haplotypic frequencies of 127 subjects were calculated using the Arlequin® v. 3.5 software. Results: We found 194 haplotypes among the studied population, 16 of which presented a frequency greater than 1%, those 16 represent 39.7% of the total haplotype diversity. All found haplotypes had been previously described in Latin American populations, 13 of the haplotypes found had been reported in Native American populations. This is the first time that an HLA genes allele and haplotypic frequencies study has been carried out in Guatemalan mixed population. The most frequently found haplotype was HLA-A*24~B*35~DRβ1*04~DQβ1*03:02 (9.06%). The allelic and haplotypic frequencies were stored on: www.allelefrequencies.net database and can be accessed under the identification number (AFND-ID: 3743). Conclusions: The results of this study constitute a valuable tool for transplantologists in Guatemala, since knowing the immunogenetics of the Guatemalan population allows them to assess better options for patients in cadaveric source programs, in order to find a compatible donor, and to evaluate in advance the immunosuppression strategies that can benefit them, according to the immunological risk that they present. It also allows to establish the initial steps for the medium-term implementation of paired donor and/or domino program, in order to exchange organs between hospitals, that will to start organ procurement programs. There are no previous works, describing HLA genes tissue typing in mestizo Guatemalan population.

Primary Thrombophilia XVII: A Narrative Review of Sticky Platelet Syndrome in México.

Sticky Platelet Syndrome (SPS) is a disorder characterized by platelet hyperaggregability, diagnosed by studying in vitro platelet aggregation with ADP and epinephrine. It is the second most common cause of thrombophilia in Mexican Mestizos and manifests as an autosomal dominant trait which, combined with other coagulopathies, contributes significantly to the morbidity and mortality of patients with primary thrombophilia. It is easily treatable with antiplatelet drugs; however, the methods for diagnosis are not readily available in all clinical laboratories and the disorder is often overlooked by most clinicians. Herein, we present the results of more than 20 years of Mexican experience with the study of SPS in a Mestizo population.

New financializations, old displacements: neo-extractivism, ‘whitening’, and consumption in Latin America

ABSTRACT The wave of Latin American left-wing governments of the 2000s claimed to have redistributed the national wealth originating from the extraction of natural resources. Termed ‘neo-extractivism’, this strategy expanded the extractive frontier and relied on the intensive exploitation of natural resources to reinvigorate welfare programs. During this period, we contend, financialization took new shapes, both in how raw materials were commercialized and in the new forms of credit and consumption enabled by the social programs institutionalized by the progressive Latin American governments during the 2000s. Indigenous, mestizo, and afro-descendant populations were the ones that confronted the expulsion produced by this economic model, displaced by the repurposing of land to expand extractive projects. We frame the ghost of empire as an instrumental metaphor to understand the concrete impacts of extractive policies, the financial relations they produced, and the racial forced displacements they generate. The ghost of empire metaphor articulates the interrelation between culture and economy, with an economic realm focused on growing state revenues via the intensive extraction of natural resources, and a cultural imagination that legitimizes the displacement and dispossession of those affected by the model in a way that inevitably reconjures the spectral forces of the colonial past.

Genetic Variations of the DPYD Gene and Its Relationship with Ancestry Proportions in Different Ecuadorian Trihybrid Populations.

Dihydropyrimidine dehydrogenase is one of the main pharmacological metabolizers of fluoropyrimidines, a group of drugs widely used in clinical oncology. Around 20 to 30% of patients treated with fluoropyrimidines experience severe toxicity caused by a partial or total decrease in enzymatic activity. This decrease is due to molecular variants in the DPYD gene. Their prevalence and allelic frequencies vary considerably worldwide, so their description in heterogeneous groups such as the Ecuadorian population will allow for the description of pharmacogenetic variants and proper characterization of this population. Thus, we genotyped all the molecular variants with a predictive value for DPYD in a total of 410 Ecuadorian individuals belonging to Mestizo, Afro-Ecuadorian, and Indigenous ethnic groups. Moreover, we developed a genetic ancestry analysis using 46 autosomal ancestry informative markers. We determined 20 genetic variations in 5 amplified regions, including 3 novel single nucleotide variants. The allele frequencies for DPYD variants c.1627G>A (*5, rs1801159), c.1129-15T>C (rs56293913), c.1218G>A (rs61622928), rs1337752, rs141050810, rs2786783, rs2811178, and g.97450142G>A (chr1, GRCh38.p13) are significantly related to Native American and African ancestry proportions. In addition, the FST calculated from these variants demonstrates the closeness between Indigenous and Mestizo populations, and evidences genetic divergence between Afro-Ecuadorian groups when compared with Mestizo and Indigenous ethnic groups. In conclusion, the genetic variability in the DPYD gene is related to the genetic component of ancestral populations in different Ecuadorian ethnic groups. The absence and low frequency of variants with predictive value for fluoropyrimidine toxicity such as DPYD *2A, HapB3, and c.2846A>T (prevalent in populations with European ancestry) is consistent with the genetic background found.

Osteoprotegerin Gene Polymorphisms Are Associated with Subclinical Atherosclerosis in the Mexican Mestizo Population.

Subclinical atherosclerosis (SA) is the presence of coronary calcification in the absence of cardiovascular symptoms, and it usually progresses to atherosclerotic disease. Studies have shown an association of osteoprotegerin gene (OPG) variants with calcification process in cardiovascular diseases; however, to this day there are no studies that evaluate individuals in the asymptomatic stage of atherosclerotic disease. Therefore, the purpose of this study was to analyze the association of four genetic variants and haplotypes of the OPG gene with the development of SA, through TaqMan genotyping assays. We also aimed to identify potential response elements for transcription factors in these genetic variants. The study included 1413 asymptomatic participants (1041 were controls and 372 were individuals with SA). The rs3102735 polymorphism appeared as a protective marker (OR = 0.693; 95% CI = 0.493–0.974; pheterozygote = 0.035; OR = 0.699; 95% CI = 0.496–0.985; pcodominant 1 = 0.040) and two haplotypes were associated with SA, one as a decreased risk: GACC (OR = 0.641, 95% CI = 0.414–0.990, p = 0.045) and another as an increased risk: GACT (OR = 1.208, 95% CI = 1.020–1.431, p = 0.029). Our data suggest a lower risk of SA in rs3102735 C carriers in a representative sample of Mexican mestizo population.

Polymorphisms of apolipoprotein E in the Afro-descendant population of Buenaventura, Colombia

ObjetivesTo estimate the frequency distribution, both allelic and genotypic, of the APOE gene in the Afro-descendant population of Buenaventura, Colombia. MethodsThree hundred and forty-eight Afro-descendant individuals were analysed and the APOE locus was genotyped by PCR-RFLP. The allelic and genotypic frequencies were established by direct counting and the Hardy-Weinberg equilibrium was evaluated through χ2 test. The frequencies obtained in this study were compared with frequencies reported for other Colombian populations through the Fisher's exact test. ResultsThe following allelic frequencies were observed: E3, 70.8%; E4, 21.4%, and E2, 7.8%. The genotypic frequencies were: E3/E3, 51.1%; E3/E4, 27.3%; E2/E3, 12.1%; E4/E4, 6%; E2/E4, 3.5%, and E2/E2, 0%. The entire examined population was found in Hardy-Weinberg equilibrium (P=.074), and significant differences were found in the allele E4 when comparing this population with the Amerindian and mestizo populations of Bogotá, Quindío, Centro-Oriente, Valle del Cauca, Barranquilla and Medellín (P≤ 0.0345). ConclusionsThe allelic frequencies observed in this study were significantly different from the frequencies reported in other Colombian populations. The high representativeness of the E4 and E2 alleles validates the hypothesis that there are micro-evolutionary processes that have been acting on their frequencies and could be associated with susceptibility to neuropsychiatric diseases such as Alzheimer's disease, metabolic alterations of fats and/or coronary artery disease.

Epistasis Between Two Gene Variants of Leptin and Vascular Endothelial Growth Factor Genes in the Development of Primary Knee Osteoarthritis.

The association of leptin (LEP) and vascular endothelial growth factor A (VEGFA) genes with the susceptibility to knee osteoarthritis (OA) has been analyzed; however, the epistasis between them has not been investigated. The objective of the study was to analyze the association of LEP and VEGFA variants and their interaction with primary knee OA in a Mexican Mestizo population. A case-control study was developed. Cases were ≥40 years, BMI ≤27 kg/m2, with primary knee OA and radiologic Grade ≥2. Controls were participants with no knee OA and a radiologic Grade < 2. The rs2167270 of LEP and rs2010963 of VEGFA were genotyped. Genotypic association was tested under codominant, dominant, and recessive models. Uni- and multi-variate analyses were developed through non-conditional logistic regression. The multifactor dimensionality reduction algorithm was developed to detect epistasis. Participants comprised 103 cases and 179 controls. Allelic and genotypic distributions did not show differences between the groups. Notwithstanding, a statistically significant interaction was observed between the LEP and VEGFA genes (p = 0.02) with a testing accuracy of 0.5199 and cross-validation consistency of 10/10. This interaction model confers an increased risk to knee OA (OR [95% CI] = 1.8 [1.1-2.9]). Interaction between LEP and VEGFA is related with genetic susceptibility to developing primary knee OA.

Copy Number Variation and Frequency of rs179008 in TLR7 Gene Associated with Systemic Lupus Erythematosus in Two Mexican Populations.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which genetic factors play a role in the susceptibility to develop it. Genes related to the synthesis of interferons such as TLR7 and genetics factors such as single nucleotide polymorphisms (SNPs) or copies number variation (CNV) in the gene have been involved with the development of the disease. The genetic differences between the populations contribute to the complexity of LES. Mexico has a mestizo population with a genetic load of at least three origins: Amerindian, Caucasian, and African. The mestizo of Yucatán is the only group whose contribution Amerindian is mainly Mayan, geographically distant from other Mexican Amerindians. We analyzed the CNV and the frequency of SNP rs179008 of the TLR7 as genetic risk factors in developing the disease in patients from Yucatán and Central Mexico. Results show that 14% of the cases of the Yucatecan population showed significantly >2 CNV and a higher risk of developing the disease (OR: 34.364), concerning 4% of those coming from Central Mexico (OR: 10.855). T allele and the A/T and T/T risk genotypes of rs179008 were more frequent in patients of Central Mexico than in those of Yucatán (50% vs. 30%, 93% vs. 30%, 4% vs. 1%), and association with susceptibility to develop SLE was observed (OR: 1.5 vs. 0.58, 9.54 vs. 0.66, 12 vs. 0.14). Data support the genetic differences between and within Mexican mestizo populations and the role of the TLR7 in the pathogenesis of SLE.

Genetic Distribution of Five Spinocerebellar Ataxia Microsatellite Loci in Mexican Native American Populations and Its Impact on Contemporary Mestizo Populations.

Spinocerebellar ataxias (SCAs) conform a heterogeneous group of neurodegenerative disorders with autosomal dominant inheritance. Five of the most frequent SCAs are caused by a CAG repeat expansion in the exons of specific genes. The SCAs incidence and the distribution of polymorphic CAG alleles vary among populations and ethnicities. Thus, characterization of the genetic architecture of ethnically diverse populations, which have undergone recent admixture and demographic events, could facilitate the identification of genetic risk factors. Owing to the great ethnic diversity of the Mexican population, this study aimed to analyze the allele frequencies of five SCA microsatellite loci (SCA1, SCA2, SCA3, SCA6, and SCA7) in eleven Mexican Native American (MNA) populations. Data from the literature were used to compare the allelic distribution of SCA loci with worldwide populations. The SCA loci allelic frequencies evidenced a certain genetic homogeneity in the MNA populations, except for Mayans, who exhibited distinctive genetic profiles. Neither pathological nor large normal alleles were found in MNA populations, except for the SCA2 pre-mutated allele in the Zapotec population. Collectively, our findings demonstrated the contribution of the MNA ancestry in shaping the genetic structure of contemporary Mexican Mestizo populations. Our results also suggest that Native American ancestry has no impact on the origin of SCAs in the Mexican population. Instead, the acquisition of pathological SCA alleles could be associated with European migration.

Frequency of CYP2D6*3 and *4 and metabolizer phenotypes in three mestizo Peruvian populations

Wild type genotypes (CYP2D6) and their allelic variants have been described in a sample of a Peruvian mestizo population. The global allele frequency was 0.015 for CYP2D6*3 and 0.051 for CYP2D6*4. The percentages of genotypes described were 97% CYP2D6*1/*1 and 3.0% CYP2D6*1/*3; 90.60% for CYP2D6*1/*1, 8.55% CYP2D6*1/*4 and 0.85% CYP2D6*4/*4. The allelic frequencies of CYP2D6*3 in the Lima subpopulations were 0.022 and 0.010 for Junin; CYP2D6*4 of 0.048, 0.060, and 0.050 for residents of Lima, Junín, and Tacna, respectively. The Hardy-Weinberg equilibrium test for the studied population showed that both frequencies are in equilibrium, p &amp;lt;.05. The metabolizer phenotype was inferred according to the genotypes: 11.54% were classified as intermediate metabolizers (*1/*3 or *1/*4) and 0.85% as poor metabolizers (*4/*4). It is concluded that the frequencies of the CYP2D6*3 and CYP2D6*4 alleles are low for the Peruvian mestizo population compared to the Latin American and tricontinental population, due to their natural population evolution, which is manifested by their decreased metabolic activity, the same that is relevant in clinical practice.