ABSTRACT
Essential Hypertension (EH) is a major global health concern, causing about 9.4 million deaths annually. Its prevalence varies across different regions, affecting 17% of the population in the Americas, 19.2% in the Western Pacific, 23.2% in Europe, 25.1% in Southeast Asia, 26.3% in the Eastern Mediterranean, and 27.2% in Africa. EH is a multifactorial disease influenced by both genetic and environmental factors. While genetic factors contribute 30-60% to blood pressure variation, the genetic complexity of EH remains largely unexplained due to limited knowledge of candidate genes and population-specific differences. Various methods, including candidate gene studies, genome-wide linkage analysis (GWLA), and genome-wide association studies (GWAS), have been employed to identify genetic factors, yet much of the heritability of EH is still unknown. This study aimed to investigate the genetic basis of EH by mapping regions of interest (ROIs) and identifying candidate genes and variants influencing EH in African-derived individuals from partially isolated populations of quilombo remnants in Vale do Ribeira, São Paulo, Brazil. Samples from 431 individuals (167 affected, 261 unaffected, 3 with unknown phenotype) from eight quilombo remnant populations were genotyped using a 650k SNP array. The global ancestry proportions were estimated at 47% African, 36% European, and 16% Native American. Genealogical information from 673 individuals was used to construct six pedigrees comprising 1104 individuals. The mapping strategy consisted of a multi-level computational approach. We constructed pedigrees based on interviews and kinship coefficient, pruned the dataset to obtain three non-overlapping markers subpanels, phased the haplotype and performed local ancestry to account for admixture. We performed GWLA and dense linkage analyses using markers subpanels and performed fine-mapping using family-based association studies (FBAS) based on population and pedigree imputed data, investigating EH-related genes and variants. The linkage analysis identified 22 ROIs with LOD scores 1.45-3.03, containing markers co-segregating with the phenotype. These ROIs encompassed 2363 genes. Fine-mapping identified 60 EH-related candidate genes and 118 suggestive or significant variants (FBAS). Among these, 14 genes, including PHGDH, S100A10, MFN2, and RYR2, were highlighted with strong evidence of association with hypertension. These genes, harboring 29 SNPs, were implicated in regulating blood pressure, sodium and potassium levels, and the aldosterone pathway. This study revealed, through a complementary approach - combining admixture-adjusted genome-wide linkage analysis based on Markov chain Monte Carlo (MCMC) methods, association studies on imputed data, and in silico investigations - genetic regions, variants and candidate genes that shed light on the genetic basis of essential hypertension, with significant potential to explain the genetic etiology in quilombo remnant populations.
ABSTRACT
Collapsing glomerulopathy (CG) is most often associated with fast progression to kidney failure with an incidence apparently higher in Brazil than in other countries. However, the reason for this occurrence is unknown. To better understand this, we performed an integrated analysis of clinical, histological, therapeutic, causative genetic and genetic ancestry data in a highly genetically admixed cohort of 70 children and adult patients with idiopathic CG (ICG). The disease onset occurred at 23 (interquartile range: 17-31) years and approximately half of patients progressed to chronic kidney disease requiring kidney replacement therapy (CKD-KRT) 36 months after diagnosis. Causative genetic bases, assessed by targeted-gene panel or whole-exome sequencing, were identified in 58.6% of patients. Among these cases, 80.5% harbored APOL1 high-risk genotypes (HRG) and 19.5% causative Mendelian variants (MV). Self-reported non-White patients more frequently had HRG. MV was an independent risk factor for progression to CKD-KRT by 36 months and the end of follow-up, while remission was an independent protective factor. All patients with HRG manifested CG at 9-44 years of age, whereas in those with APOL1 low-risk genotype, the disease arose throughout life. HRGs were associated with higher proportion of African genetic ancestry. Novel causative MVs were identified in COL4A5, COQ2 and PLCE1 and previously described causative MVs were identified in MYH9, TRPC6, COQ2, COL4A3 and TTC21B. Three patients displayed HRG combined with a variant of uncertain significance (ITGB4, LAMA5 or PTPRO). MVs were associated with worse kidney prognosis. Thus, our data reveal that the genetic status plays a major role in ICG pathogenesis, accounting for more than half of cases in a highly admixed Brazilian population.
Subject(s)
Apolipoprotein L1 , Renal Insufficiency, Chronic , Adult , Child , Humans , Apolipoprotein L1/genetics , Genotype , Kidney/pathology , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/genetics , Renal Insufficiency, Chronic/pathology , Risk Factors , Adolescent , Young AdultABSTRACT
Ecological conditions in the Amazon rainforests are historically favorable for the transmission of numerous tropical diseases, especially vector-borne diseases. The high diversity of pathogens likely contributes to the strong selective pressures for human survival and reproduction in this region. However, the genetic basis of human adaptation to this complex ecosystem remains unclear. This study investigates the possible footprints of genetic adaptation to the Amazon rainforest environment by analyzing the genomic data of 19 native populations. The results based on genomic and functional analysis showed an intense signal of natural selection in a set of genes related to Trypanosoma cruzi infection, which is the pathogen responsible for Chagas disease, a neglected tropical parasitic disease native to the Americas that is currently spreading worldwide.
Subject(s)
Chagas Disease , Trypanosoma cruzi , Humans , Trypanosoma cruzi/genetics , Ecosystem , Chagas Disease/genetics , Chagas Disease/parasitology , Indigenous PeoplesABSTRACT
OBJECTIVES: The X-chromosome contains the largest number of immune-related genes, which play a major role in COVID-19 symptomatology and susceptibility. Here, we had a unique opportunity to investigate, for the first time, COVID-19 outcomes in six unvaccinated young Brazilian patients with Turner syndrome (TS; 45, X0), including one case of critical illness in a child aged 10 years, to evaluate their immune response according to their genetic profile. METHODS: A serological analysis of humoral immune response against SARS-CoV-2, phenotypic characterization of antiviral responses in peripheral blood mononuclear cells after stimuli, and the production of cytotoxic cytokines of T lymphocytes and natural killer cells were performed in blood samples collected from the patients with TS during the convalescence period. Whole exome sequencing was also performed. RESULTS: Our volunteers with TS showed a delayed or insufficient humoral immune response to SARS-CoV-2 (particularly immunoglobulin G) and a decrease in interferon-γ production by cluster of differentiation (CD)4+ and CD8+ T lymphocytes after stimulation with toll-like receptors 7/8 agonists. In contrast, we observed a higher cytotoxic activity in the volunteers with TS than the volunteers without TS after phorbol myristate acetate/ionomycin stimulation, particularly granzyme B and perforin by CD8+ and natural killer cells. Interestingly, two volunteers with TS carry rare genetic variants in genes that regulate type I and III interferon immunity. CONCLUSION: Following previous reports in the literature for other conditions, our data showed that patients with TS may have an impaired immune response against SARS-CoV-2. Furthermore, other medical conditions associated with TS could make them more vulnerable to COVID-19.
Subject(s)
COVID-19 , Turner Syndrome , Child , Humans , SARS-CoV-2 , Turner Syndrome/complications , Turner Syndrome/genetics , Leukocytes, Mononuclear , CD8-Positive T-Lymphocytes , Antibodies, ViralABSTRACT
The inference of genetic ancestry plays an increasingly prominent role in clinical, population, and forensic genetics studies. Several genotyping strategies and analytical methodologies have been developed over the last few decades to assign individuals to specific biogeographic regions. However, despite these efforts, ancestry inference in populations with a recent history of admixture, such as those in Brazil, remains a challenge. In admixed populations, proportion and components of genetic ancestry vary on different levels: (i) between populations; (ii) between individuals of the same population, and (iii) throughout the individual's genome. The present study evaluated 1171 admixed Brazilian samples to compare the genetic ancestry inferred by tri-/tetra-hybrid admixture models and evaluated different marker sets from those with small numbers of ancestry informative markers panels (AIMs), to high-density SNPs (HDSNP) and whole-genome-sequence (WGS) data. Analyses revealed greater variation in the correlation coefficient of ancestry components within and between admixed populations, especially for minority ancestral components. We also observed positive correlation between the number of markers in the AIMs panel and HDSNP/WGS. Furthermore, the greater the number of markers, the more accurate the tri-/tetra-hybrid admixture models.
Subject(s)
Genetics, Population , Humans , Brazil , Minority Groups , Polymorphism, Single Nucleotide , South American People/genetics , Whole Genome SequencingABSTRACT
BACKGROUND: Although older adults are at a high risk of severe or critical Covid-19, there are many cases of unvaccinated centenarians who had a silent infection or recovered from mild or moderate Covid-19. We studied three Brazilian supercentenarians, older than 110 years, who survived Covid-19 in 2020 before being vaccinated. RESULTS: Despite their advanced age, humoral immune response analysis showed that these individuals displayed robust levels of IgG and neutralizing antibodies (NAbs) against SARS-CoV-2. Enrichment of plasma proteins and metabolites related to innate immune response and host defense was also observed. None presented autoantibodies (auto-Abs) to type I interferon (IFN). Furthermore, these supercentenarians do not carry rare variants in genes underlying the known inborn errors of immunity, including particular inborn errors of type I IFN. CONCLUSION: These observations suggest that their Covid-19 resilience might be a combination of their genetic background and their innate and adaptive immunity.
ABSTRACT
Background: Although aging correlates with a worse prognosis for Covid-19, super elderly still unvaccinated individuals presenting mild or no symptoms have been reported worldwide. Most of the reported genetic variants responsible for increased disease susceptibility are associated with immune response, involving type I IFN immunity and modulation; HLA cluster genes; inflammasome activation; genes of interleukins; and chemokines receptors. On the other hand, little is known about the resistance mechanisms against SARS-CoV-2 infection. Here, we addressed polymorphisms in the MHC region associated with Covid-19 outcome in super elderly resilient patients as compared to younger patients with a severe outcome. Methods: SARS-CoV-2 infection was confirmed by RT-PCR test. Aiming to identify candidate genes associated with host resistance, we investigated 87 individuals older than 90 years who recovered from Covid-19 with mild symptoms or who remained asymptomatic following positive test for SARS-CoV-2 as compared to 55 individuals younger than 60 years who had a severe disease or died due to Covid-19, as well as to the general elderly population from the same city. Whole-exome sequencing and an in-depth analysis of the MHC region was performed. All samples were collected in early 2020 and before the local vaccination programs started. Results: We found that the resilient super elderly group displayed a higher frequency of some missense variants in the MUC22 gene (a member of the mucins' family) as one of the strongest signals in the MHC region as compared to the severe Covid-19 group and the general elderly control population. For example, the missense variant rs62399430 at MUC22 is two times more frequent among the resilient super elderly (p = 0.00002, OR = 2.24). Conclusion: Since the pro-inflammatory basal state in the elderly may enhance the susceptibility to severe Covid-19, we hypothesized that MUC22 might play an important protective role against severe Covid-19, by reducing overactive immune responses in the senior population.
Subject(s)
COVID-19 , Aged , Humans , Brazil/epidemiology , COVID-19/epidemiology , COVID-19/genetics , Genes, MHC Class II , HLA-A Antigens , SARS-CoV-2/geneticsABSTRACT
In his 1972 paper 'The apportionment of human diversity', Lewontin showed that, when averaged over loci, genetic diversity is predominantly attributable to differences among individuals within populations. However, selection can alter the apportionment of diversity of specific genes or genomic regions. We examine genetic diversity at the human leucocyte antigen (HLA) loci, located within the major histocompatibility complex (MHC) region. HLA genes code for proteins that are critical to adaptive immunity and are well-documented targets of balancing selection. The single-nucleotide polymorphisms (SNPs) within HLA genes show strong signatures of balancing selection on large timescales and are broadly shared among populations, displaying low FST values. However, when we analyse haplotypes defined by these SNPs (which define 'HLA alleles'), we find marked differences in frequencies between geographic regions. These differences are not reflected in the FST values because of the extreme polymorphism at HLA loci, illustrating challenges in interpreting FST. Differences in the frequency of HLA alleles among geographic regions are relevant to bone-marrow transplantation, which requires genetic identity at HLA loci between patient and donor. We discuss the case of Brazil's bone marrow registry, where a deficit of enrolled volunteers with African ancestry reduces the chance of finding donors for individuals with an MHC region of African ancestry. This article is part of the theme issue 'Celebrating 50 years since Lewontin's apportionment of human diversity'.
Subject(s)
Major Histocompatibility Complex , Polymorphism, Single Nucleotide , Alleles , Gene Frequency , Haplotypes , Humans , Major Histocompatibility Complex/geneticsABSTRACT
As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enables identification of ~2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS.
Subject(s)
Genomics , Metagenomics , Aged , Brazil/epidemiology , Genome, Human/genetics , Genomics/methods , Humans , Polymorphism, Single Nucleotide , Whole Genome SequencingABSTRACT
Recurrence of COVID-19 in recovered patients has been increasingly reported. However, the immune mechanisms behind the recurrence have not been thoroughly investigated. The presence of neutralizing antibodies (nAbs) in recurrence/reinfection cases suggests that other types of immune response are involved in protection against recurrence. Here, we investigated the innate type I/III interferon (IFN) response, binding and nAb assays and T-cell responses to severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) with IFN gamma (IFNγ) enzyme-linked spot assay (ELISPOT) in three pairs of young adult monozygotic (MZ) twins with previous confirmed COVID-19, one of them presenting a severe recurrence four months after the initial infection. Twin studies have been of paramount importance to comprehend the immunogenetics of infectious diseases. Each MZ twin pair was previously exposed to SARS-CoV-2, as seen by clinical reports. The six individuals presented similar overall recovered immune responses except for the recurrence case, who presented a drastically reduced number of recognized SARS-CoV-2 T-cell epitopes on ELISPOT as compared to her twin sister and the other twin pairs. Our results suggest that the lack of a broad T-cell response to initial infection may have led to recurrence, emphasizing that an effective SARS-CoV-2-specific T-cell immune response is key for complete viral control and avoidance of clinical recurrence of COVID-19.
Subject(s)
COVID-19/immunology , Epitopes, T-Lymphocyte/immunology , Immunity, Cellular , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Twins, Monozygotic , Adolescent , Adult , Female , Humans , Male , RecurrenceABSTRACT
We recently described a novel missense variant [c.2090T>G:p.(Leu697Trp)] in the MYO3A gene, found in two Brazilian families with late-onset autosomal dominant nonsyndromic hearing loss (ADNSHL). Since then, with the objective of evaluating its contribution to ADNSHL in Brazil, the variant was screened in additional 101 pedigrees with probable ADNSHL without conclusive molecular diagnosis. The variant was found in three additional families, explaining 3/101 (~3%) of cases with ADNSHL in our Brazilian pedigree collection. In order to identify the origin of the variant, 21 individuals from the five families were genotyped with a high-density SNP array (~600 K SNPs- Axiom Human Origins; ThermoFisher). The identity by descent (IBD) approach revealed that many pairs of individuals from the different families have a kinship coefficient equivalent to that of second cousins, and all share a minimum haplotype of ~607 kb which includes the c.2090T>G variant suggesting it probably arose in a common ancestor. We inferred that the mutation occurred in a chromosomal segment of European ancestry and the time since the most common ancestor was estimated in 1100 years (CI = 775-1425). This variant was also reported in a Dutch family, which shares a 87,121 bp haplotype with the Brazilian samples, suggesting that Dutch colonists may have brought it to Northeastern Brazil in the 17th century. Therefore, the present study opens new avenues to investigate this variant not only in Brazilians but also in European families with ADNSHL.
Subject(s)
Gene Frequency , Hearing Loss, Sensorineural/genetics , Myosin Heavy Chains/genetics , Myosin Type III/genetics , Brazil , Founder Effect , Genes, Dominant , Haplotypes , Human Migration , Humans , Mutation, Missense , Pedigree , Polymorphism, Single NucleotideABSTRACT
South America is home to one of the most culturally diverse present-day native populations. However, the dispersion pattern, genetic substructure, and demographic complexity within South America are still poorly understood. Based on genome-wide data of 58 native populations, we provide a comprehensive scenario of South American indigenous groups considering the genomic, environmental, and linguistic data. Clear patterns of genetic structure were inferred among the South American natives, presenting at least four primary genetic clusters in the Amazonian and savanna regions and three clusters in the Andes and Pacific coast. We detected a cline of genetic variation along a west-east axis, contradicting a hard Andes-Amazon divide. This longitudinal genetic variation seemed to have been shaped by both serial population bottlenecks and isolation by distance. Results indicated that present-day South American substructures recapitulate ancient macroregional ancestries and western Amazonia groups show genetic evidence of cultural exchanges that led to language replacement in precontact times. Finally, demographic inferences pointed to a higher resilience of the western South American groups regarding population collapses caused by the European invasion and indicated precontact population reductions and demic expansions in South America.
Subject(s)
Genetics, Population , Genomics , Genetic Variation , Humans , Indians, South American/genetics , Indigenous Peoples , South America , American Indian or Alaska NativeSubject(s)
Child, Preschool , Child , Physical Therapy Modalities , Nocturnal Enuresis , Urinary Tract , Child Health , EnuresisABSTRACT
Despite the high number of individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) symptoms worldwide, many exposed individuals remain asymptomatic and/or uninfected and seronegative. This could be explained by a combination of environmental (exposure), immunological (previous infection), epigenetic, and genetic factors. Aiming to identify genetic factors involved in immune response in symptomatic COVID-19 as compared to asymptomatic exposed individuals, we analyzed 83 Brazilian couples where one individual was infected and symptomatic while the partner remained asymptomatic and serum-negative for at least 6 months despite sharing the same bedroom during the infection. We refer to these as "discordant couples". We performed whole-exome sequencing followed by a state-of-the-art method to call genotypes and haplotypes across the highly polymorphic major histocompatibility complex (MHC) region. The discordant partners had comparable ages and genetic ancestry, but women were overrepresented (65%) in the asymptomatic group. In the antigen-presentation pathway, we observed an association between HLA-DRB1 alleles encoding Lys at residue 71 (mostly DRB1*03:01 and DRB1*04:01) and DOB*01:02 with symptomatic infections and HLA-A alleles encoding 144Q/151R with asymptomatic seronegative women. Among the genes related to immune modulation, we detected variants in MICA and MICB associated with symptomatic infections. These variants are related to higher expression of soluble MICA and low expression of MICB. Thus, quantitative differences in these molecules that modulate natural killer (NK) activity could contribute to susceptibility to COVID-19 by downregulating NK cell cytotoxic activity in infected individuals but not in the asymptomatic partners.
Subject(s)
Asymptomatic Infections , COVID-19 , Histocompatibility Antigens , Major Histocompatibility Complex , SARS-CoV-2 , Adult , Aged , Brazil , COVID-19/genetics , COVID-19/immunology , Female , Genetic Predisposition to Disease , Genotype , Histocompatibility Antigens/genetics , Histocompatibility Antigens/immunology , Humans , Major Histocompatibility Complex/genetics , Major Histocompatibility Complex/immunology , Male , Middle Aged , Exome SequencingABSTRACT
Meeting the challenges brought by the COVID-19 pandemic requires an interdisciplinary approach. In this context, integrating knowledge of immune function with an understanding of how genetic variation influences the nature of immunity is a key challenge. Immunogenetics can help explain the heterogeneity of susceptibility and protection to the viral infection and disease progression. Here, we review the knowledge developed so far, discussing fundamental genes for triggering the innate and adaptive immune responses associated with a viral infection, especially with the SARS-CoV-2 mechanisms. We emphasize the role of the HLA and KIR genes, discussing what has been uncovered about their role in COVID-19 and addressing methodological challenges of studying these genes. Finally, we comment on questions that arise when studying admixed populations, highlighting the case of Brazil. We argue that the interplay between immunology and an understanding of genetic associations can provide an important contribution to our knowledge of COVID-19.
ABSTRACT
Pyruvate kinase (PK), encoded by the PKLR gene, is a key player in glycolysis controlling the integrity of erythrocytes. Due to Plasmodium selection, mutations for PK deficiency, which leads to hemolytic anemia, are associated with resistance to malaria in sub-Saharan Africa and with susceptibility to intracellular pathogens in experimental models. In this case-control study, we enrolled 4,555 individuals and investigated whether PKLR single nucleotide polymorphisms (SNPs) putatively selected for malaria resistance are associated with susceptibility to leprosy across Brazil (Manaus-North; Salvador-Northeast; Rondonópolis-Midwest and Rio de Janeiro-Southeast) and with tuberculosis in Mozambique. Haplotype T/G/G (rs1052176/rs4971072/rs11264359) was associated with leprosy susceptibility in Rio de Janeiro (OR = 2.46, p = 0.00001) and Salvador (OR = 1.57, p = 0.04), and with tuberculosis in Mozambique (OR = 1.52, p = 0.07). This haplotype downregulates PKLR expression in nerve and skin, accordingly to GTEx, and might subtly modulate ferritin and haptoglobin levels in serum. Furthermore, we observed genetic signatures of positive selection in the HCN3 gene (xpEHH>2 -recent selection) in Europe but not in Africa, involving 6 SNPs which are PKLR/HCN3 eQTLs. However, this evidence was not corroborated by the other tests (FST, Tajima's D and iHS). Altogether, we provide evidence that a common PKLR locus in Africans contribute to mycobacterial susceptibility in African descent populations and also highlight, for first, PKLR as a susceptibility gene for leprosy and TB.
Subject(s)
Malaria/genetics , Polymorphism, Single Nucleotide , Pyruvate Kinase/genetics , Adult , Brazil , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Haplotypes , Humans , Linkage Disequilibrium , Logistic Models , Male , Middle Aged , Mozambique , Pyruvate Kinase/deficiency , Young AdultABSTRACT
Investigation of human genes under pathogen-driven selection as Plasmodium sp. has pinpointed genetic variants that participate in the adaptation to the environment and/or are related to severities of human diseases. The current study examined an example of an evolutionary trade-off in which genetic variants in the PKLR gene putatively selected for malaria resistance influence the susceptibility to mycobacterial diseases (leprosy and tuberculosis) in Brazilian population and Mozambique. A complete characterization of the biological effect of those risk variants may clarify the role of the PKLR gene in leprosy and tuberculosis. Deciphering the genetic basis of mycobacterial diseases has implications for the identification of true high-risk individuals in order to optimize screening strategies. Furthermore, the trade-off mechanism discussed in this work might occur in other central genes of immune response and biochemical pathways, controlling the susceptibility to other infectious diseases.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Pyruvate Kinase/genetics , Polymorphism, Single Nucleotide , Malaria/genetics , Mozambique , Haplotypes , Brazil , Genetic Predisposition to Disease , Gene FrequencyABSTRACT
Introdução: As características morfológicas do pé sugerem desalinhamento dos membros inferiores, tornando praticantes de corrida mais susceptíveis a dor e lesões. Objetivo: Analisar a prevalência de dor e comparar as características morfológicas dos pés e alinhamento do retropé entre corredoras com sintomas no joelho e assintomáticas. Métodos: Estudo caso-controle, exploratório com abordagem quantitativa, com 31 mulheres corredoras. A presença de dor e lesões foi avaliada por meio de um questionário padronizado. A morfologia dos pés foi realizada através da inspeção, com registros fotográficos no plano posterior e o arco longitudinal do pé foi analisado através de podometria de pressão. Os dados foram analisados pelo SPSS versão 18.0. Na comparação das médias das variáveis dos ângulos de retropé foi utilizado o teste t Student para amostras independentes, considerando o p < 0,05. Resultados: Observouse que 86% das mulheres relataram sintoma predominante no joelho (64,51%). Na análise das características morfológicas dos pés, encontrou-se predomínio do tipo rebaixado e assimetria dos retropés no grupo sintomático. Conclusão: Apenas a assimetria entre os membros e as caraterísticas morfológicas do pé apresentam associação com a presença de dor no joelho. (AU)
Introduction: The morphological characteristics of foot suggests lower limbs misalignment, making street runners more susceptible to pain. Objective: To compare the morphological characteristics of the foot and rearfoot alignment between runners with or without knee symptoms, as well as to analyze the prevalence of pain. Methods: Case-control, exploratory and quantitative approach study, with 30 female runners. The presence of pain and lesions was evaluated by a standardized questionnaire. Foot morphology was analyzed through inspection, with photographic records in the posterior plane, and the longitudinal arch of the foot was measured by pressure podometry. The data were analyzed by SPSS 18.0. In the comparison of the means of the variables of the hindfoot angles, the Student t test was used for independent samples, considering p < 0.05. Results: We observed that 86% of the women reported a symptom, predominant in the knee (64.51%). In the analysis of the foot morphological characteristics, we found a predominance of the recessed type and asymmetry of the symptomatic group backs. Conclusion: Asymmetry between the limbs and morphological features of the foot are associated with knee pain. (AU)