Genomic investigation on genes related to mercury metabolism in Amazonian indigenous populations.

Studies have identified elevated levels of mercury in Amazonian Indigenous individuals, highlighting them as one of the most exposed to risks. In the unique context of the Brazilian Indigenous population, it is crucial to identify genetic variants with clinical significance to better understand vulnerability to mercury and its adverse effects. Currently, there is a lack of research on the broader genomic profile of Indigenous people, particularly those from the Amazon region, concerning mercury contamination. Therefore, the aim of this study was to assess the genomic profile related to the processes of mercury absorption, distribution, metabolism, and excretion in 64 Indigenous individuals from the Brazilian Amazon. We aimed to determine whether these individuals exhibit a higher susceptibility to mercury exposure. Our study identified three high-impact variants (GSTA1 rs1051775, GSTM1 rs1183423000, and rs1241704212), with the latter two showing a higher frequency in the study population compared to global populations. Additionally, we discovered seven new variants with modifier impact and a genomic profile different from the worldwide populations. These genetic variants may predispose the study population to more harmful mercury exposure compared to global populations. As the first study to analyze broader genomics of mercury metabolism pathways in Brazilian Amazonian Amerindians, we emphasize that our research aims to contribute to public policies by utilizing genomic investigation as a method to identify populations with a heightened susceptibility to mercury exposure.

Cognitive performance and all-cause mortality in community dwellers of Amerindian ancestry living in rural Ecuador: A population-based, longitudinal prospective study.

OBJECTIVE: There is limited information on mortality risk in individuals with cognitive impairment living in rural Latin America. In this study, we assess the association between cognitive impairment and all-cause mortality in adults of Amerindian ancestry living in rural Ecuador. PATIENTS AND METHODS: Middle-aged and older adults enrolled in the population-based Three Villages Study cohort were followed prospectively in order to estimate mortality risk according to their baseline cognitive performance as determined by the Montreal Cognitive Assessment (MoCA). Results were adjusted for demographics, level of education, traditional cardiovascular risk factors, symptoms of depression, severe tooth loss, and oily fish intake (factors previously associated with mortality in the study population). RESULTS: Analysis included 1022 individuals followed for an average of 7.8 ± 3.4 years. Mean MoCA score was 21.2 ± 5.4 points (median: 22 points), with 334 (32.7%) individuals showing cognitive impairment, as evidenced by a MoCA score ≤ 19 points (the cutoff for poor cognitive performance based on previous studies in the same population). A total of 150 (14.7%) individuals died during the follow-up. Crude mortality rate was 2.87 per 100 person-years (95% C.I.: 2.08 - 3.96). For individuals with normal cognition, the mortality rate was 1.21 (95% C.I.: 0.92 - 1.50) while for those with cognitive impairment the rate increased to 3.48 (95% C.I.: 2.73 - 4.23). A multivariate Cox-proportional hazards model, confirmed that individuals with cognitive impairment had a significantly higher mortality risk than those without cognitive impairment (HR: 1.52; 95% C.I.: 1.05 - 2.18). CONCLUSIONS: Cognitive impairment is associated with mortality in the study population.

Differential NRAMP1gene's D543N genotype frequency: Increased risk of contracting tuberculosis among Venezuelan populations.

NRAMP1 and VDR gene polymorphisms have been variably associated with susceptibility to tuberculosis (TB) amongst populations having different genetic background. NRAMP1 and VDR gene variants' association with susceptibility to active infection by Mycobacterium tuberculosis (Mtb) was analyzed in the Warao Amerindian population, an ethnic population from Venezuela's Orinoco delta region. Genomic DNA was extracted from individuals with and without TB to evaluate genetic polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Four NRAMP1 gene polymorphisms were analyzed: D543N (rs17235409), 3' UTR (rs17235416), INT4 (rs3731865), and 274C/T (rs2276631), and one VDR gene polymorphism: FokI (rs2228570). The results showed that the genotypes D543N-A/A, 3'UTR-TGTG+/+, INT4-C/C, and 274C/T-T/T of known polymorphism in the NRAMP1 gene, as well as the genotypes FokI-F/f and FokI-f/f in the VDR gene were most often found in indigenous Warao with active TB. Binomial logistic regression was used for evaluating associations between polymorphisms and risk of contracting TB, an association between NRAMP1-D543N-A/A genotype distribution and TB susceptibility was found in Warao Amerindians. Regarding Venezuelan populations having different genetic backgrounds; statistically significant TB associations concerning NRAMP1-D543N-A/A, INT4-C/C and 3'UTR-TGTG+/+ variant genotype distributions in Warao Amerindians (indigenous) compared to Creole (admixed non-indigenous population) individuals were found. In conclusion, the results thus indicated that the association between NRAMP1-D543N-A/A genotype and TB in Warao Amerindians could support such allele's role in host susceptibility to Mtb infection.

Distribution of a novel CYP2C haplotype in Native American populations.

The CYP2C19 gene, located in the CYP2C cluster, encodes the major drug metabolism enzyme CYP2C19. This gene is highly polymorphic and no-function (CYP2C19*2 and CYP2C19*3), reduced function (CYP2C19*9) and increased function (CYP2C19*17) star alleles (haplotypes) are commonly used to predict CYP2C19 metabolic phenotypes. CYP2C19*17 and the genotype-predicted rapid (RM) and ultrarapid (UM) CYP2C19 metabolic phenotypes are absent or rare in several Native American populations. However, discordance between genotype-predicted and pharmacokinetically determined CYP2C19 phenotypes in Native American cohorts have been reported. Recently, a haplotype defined by rs2860840T and rs11188059G alleles in the CYP2C cluster has been shown to encode increased rate of metabolism of the CYP2C19 substrate escitalopram, to a similar extent as CYP2C19*17. We investigated the distribution of the CYP2C:TG haplotype and explored its potential impact on CYP2C19 metabolic activity in Native American populations. The study cohorts included individuals from the One Thousand Genomes Project AMR superpopulation (1 KG_AMR), the Human Genome Diversity Project (HGDP), and from indigenous populations living in Brazil (Kaingang and Guarani). The frequency range of the CYP2C:TG haplotype in the study cohorts, 0.469 to 0.598, is considerably higher than in all 1 KG superpopulations (range: 0.014-to 0.340). We suggest that the high frequency of the CYP2C:TG haplotype might contribute to the reported discordance between CYP2C19-predicted and pharmacokinetically verified CYP2C19 metabolic phenotypes in Native American cohorts. However, functional studies involving genotypic correlations with pharmacokinetic parameters are warranted to ascertain the importance of the CYP2C:TG haplotype.

HLA-DMB alleles and haplotypes in Ecuador (Cuenca) Amerindians: Importance for HLA and disease studies.

HLA-DMB allele frequencies and HLA-DBM-DRB1-DQB1 extended haplotypes were studied for the first time in Amerindians (Cuenca city area, Ecuador). It was found that most common extended haplotypes gathered the most frequent HLA-DRB1 Amerindian alleles. HLA-DMB polymorphism studies may be important to uncover HLA and diseases pathogenesis and also in an extended HLA haplotype frameshift. HLA-DM molecule has a crucial role together with CLIP protein in HLA class II peptide presentation. HLA extended haplotypes including complement and non classical genes alleles are proposed to HLA and disease studies.

HLA study in Mexico Nahua/Aztec Amerindians: Close relatedness to the ancient Central America ethnic groups.

Nahua population (also named Aztec or Mexica) was studied for HLA class II genes in a Mexican rural city (Santo Domingo Ocotitlan, Morelos State) belonging to the nowadays Náhuatl speaking areas in Mexico. The most frequent HLA class II alleles were typical Amerindian (HLA-DRB1*04:07, DQB1*03:01 DRB1*04:03 or DRB1*04:04) and also were some calculated extended haplotypes (HLA-DRB1*04:07-DQB1*03:02,DRB1*08:02-DQB1*04:02, or DRB1*10:01-DQB1*05:01 among others). When using HLA-DRB1 Neís genetic distances, our isolated Nahua population was found to be close to other Central America Amerindians like the ancient-established Mayans or Mixe. This may suggest that Nahuas origin was also from Central America. It contrasts to legend that assumes they came from the North, and they built the Aztec Empire after submitting Central America neighbouring ethnic groups before 1519 CE when Spaniards led by Hernán Cortés arrived to Mexico.

Dietary oily fish intake reduces the risk of all-cause mortality in frequent fish consumers of Amerindian ancestry living in coastal Ecuador: the Atahualpa project.

PURPOSE: To assess the relationship between dietary oily fish intake and all-cause mortality in a population of frequent fish consumers of Amerindian ancestry living in rural Ecuador. METHODS: Individuals aged ≥ 40 years enrolled in the prospective population-based Atahualpa Project cohort received annual questionnaires to estimate their dietary oily fish intake. Only fish served broiled or cooked in the soup were included for analysis. Poisson regression and Cox-proportional hazards models adjusted for demographics, education level and cardiovascular risk factors were obtained to estimate mortality risk according to the amount of oily fish intake stratified in tertiles. RESULTS: Analysis included 909 individuals (mean age: 55.1 ± 12.8 years) followed by a median of 7.5 ± 3 years. Mean oily fish intake was 9.4 ± 5.7 servings per week. A total of 142 (16%) individuals died during the follow-up. The mortality rate for individuals in the first tertile de oily fish intake (0.0-6.29 servings) was 2.87 per 100 person-years, which decreased to 1.78 for those in the third tertile (10.59-35.0 servings). An adjusted Cox-proportional hazards model showed that individuals allocated to the second (HR 0.61; 95% CI 0.41-0.92) and third (HR 0.60; 95% CI 0.40-0.91) tertiles of dietary oily fish intake had significantly lower mortality risk than those in the first tertile. CONCLUSION: Sustained oily fish intake of more than six servings per week reduces mortality risk in middle-aged and older adults of Amerindian ancestry.

Full-length characterization of the HLA-DQB1*03:25:01 allele in two Amerindian individuals.

Genomic full-length characterization of the HLA-DQB1*03:25:01 allele.

Health professionals and Amerindian patients: representations and practices in French Guiana / Professionnels de santé et patients amérindiens : représentations et pratiques en Guyane française

CONTEXT: In French Guiana, Amerindian populations find themselves in a health system whose therapeutic itinerary revolves around their traditional medicine and modern medicine provided by health professionals mostly from hexagonal France. The latter intervene in a “complexity of intercultural contact” which influences the caregiver-patient relationship and affects therapeutic adherence. METHOD: To better understand the practices and representations of the health system in an intercultural context, qualitative research was carried out in the field between 2018 and 2019 with seventeen health professionals working in health centers located in the municipalities of the Interior of French Guiana. Semi-structured individual interviews were conducted in order to explore the representations, the difficulties encountered, and the tools used by these caregivers in their daily practice. These interviews were crossed with participant observations and bibliographical research in the medical and anthropological fields. RESULTS: The caregiver-patient encounter was asymmetrical, unequal and was part of a power relationship. The caregivers remained marked by ethnocentric representations -inherent to each culture- far removed from those of the populations and this divergence impacted the practice. DISCUSSION: It would be advisable to shift the focus in order to « penetrate » the frame of reference of the Other and rebalance relationships. The exploration of popular knowledge and skills and the application of proven teaching methods would encourage therapeutic adherence. « Homethnic workers » and intercultural training could help promote community health.

Contexte: En Guyane française, les populations amérindiennes se retrouvent dans un système de santé dont l'itinéraire thérapeutique s'articule autour de leur médecine traditionnelle et d'une médecine moderne prodiguée par des professionnels de santé originaires, pour la plupart, de la France hexagonale. Ces derniers interviennent dans une « complexité de contact interculturel ¼ qui influence la relation soignant soigné et affecte l'adhésion thérapeutique. Méthode: Pour mieux comprendre les représentations et pratiques du système de santé en contexte interculturel, une recherche qualitative a été menée sur le terrain, en 2018 et 2019, auprès de dix-sept professionnels de santé exerçant dans les centres de santé situés dans les communes de l'Intérieur de la Guyane. Des entretiens individuels semi-structurés ont été menés afin d'explorer les représentations, les difficultés rencontrées et les outils mobilisés par ces soignants dans leur pratique courante. Ces entretiens ont été croisés avec des observations participantes et des recherches bibliographiques dans les champs médicaux et anthropologiques. Résultats: La rencontre soignant soigné était asymétrique, inégale et s'inscrivait dans un rapport de pouvoir. Les soignants restaient marqués de représentations ethnocentriques - inhérentes à chaque culture - éloignées de celles des populations amérindiennes, et cette divergence impactait la pratique. Discussion: Il conviendrait de se décentrer, pour « pénétrer ¼ dans le cadre de référence de l'Autre et rééquilibrer les rapports. L'exploration des savoirs et savoir-faire populaires et l'application de méthodes éprouvées d'enseignement encourageraient l'adhésion thérapeutique. Les « intervenants homethniques ¼ et une formation à l'interculturalité pourraient favoriser la promotion de la santé communautaire.

The effect of previous strokes on the relationship between ankle-brachial index determinations and incident strokes: A population-based, longitudinal prospective study in older adults.

OBJECTIVE: Abnormal ankle-brachial index (ABI) determinations may be associated with an increased risk of incident strokes. However, the impact of previous strokes in this relationship is unknown. We estimated the role of previous strokes on the association between abnormal ABI determinations and incident stroke risk in community-dwelling older adults. METHODS: Atahualpa residents aged ≥60 years received ABI determinations, cardiovascular risk factors assessment, and brain MRIs. ABIs were classified as abnormal if ≤0.9 or ≥1.4. Incident strokes were diagnosed by a certified neurologist with the aid of a post-event MRI. Poisson regression models were fitted to estimate stroke incidence rate ratio (IRR) according to categories of ABI. RESULTS: Analysis included 389 participants (mean age: 68.2 ± 8.1 years). Eighty-six persons (22%) had abnormal ABI determinations. Incident strokes occurred in 38 (9.8%) individuals after a mean follow-up of 6.1 ± 1.9 years. Abnormal ABIs were associated with incident strokes in unadjusted analyses (p = 0.002) as well as in a Poisson regression model adjusted for demographics and clinical covariates (IRR: 2.57; 95% C.I.: 1.29-5.13), but not when the model was adjusted for neuroimaging covariates (IRR: 1.46; 95% C.I.: 0.67-3.20). Interaction models showed that having both abnormal ABI and non-lacunar strokes at baseline made the individual 9.7 times more likely to have an incident stroke (95% C.I.: 3.87-24.4). The risk was reduced to 2.2 (95% C.I.: 0.96-5.13) for those who only had an abnormal ABI. CONCLUSIONS: An abnormal ABI is associated with a doubling the risk of incident strokes, but its importance is superseded by history of non-lacunar strokes.

Patterns of progression of cerebral small vessel disease markers in older adults of Amerindian ancestry: a population-based, longitudinal prospective cohort study.

BACKGROUND: Progression of cerebral small vessel disease (cSVD) markers has been studied in different races/ethnic groups. However, information from individuals of Amerindian ancestry is lacking. We sought to evaluate progression patterns of cSVD markers in community-dwelling older adults of Amerindian ancestry. METHODS: Following a longitudinal prospective study design, participants of the Atahualpa Project Cohort aged ≥ 60 years received a baseline brain MRI and clinical interviews. Those who also received a brain MRI at the end of the study were included. Poisson regression models were fitted to assess cSVD markers progression according to their baseline load after a median follow-up of 6.5 ± 1.4 years. Logistic regression models were fitted to assess interrelations in the progression of the different cSVD markers at the end of the study. RESULTS: The study included 263 individuals (mean age: 65.7 ± 6.2 years). Progression of white matter hyperintensities (WMH) was noticed in 103 (39%) subjects, cerebral microbleeds in 25 (12%), lacunes in 12 (5%), and enlarged basal ganglia-perivascular spaces (BG-PVS) in 56 (21%). Bivariate Poisson regression models showed significant associations between WMH severity at baseline and progression of WMH and enlarged BG-PVS. These associations became non-significant in multivariate models adjusted for clinical covariates. Logistic regression models showed interrelated progressions of WMH, cerebral microbleeds and enlarged BG-PVS. The progression of lacunes was independent. CONCLUSIONS: Patterns of cSVD marker progression in this population of Amerindians are different than those reported in other races/ethnic groups. The independent progression of lacunes suggests different pathogenic mechanisms with other cSVD markers.

Exome Evaluation of Autism-Associated Genes in Amazon American Populations.

Autism spectrum disorder is a neurodevelopmental disorder, affecting one in 160 children worldwide. The causes of autism are still poorly understood, but research shows the relevance of genetic factors in its pathophysiology, including the CHD8, SCN2A, FOXP1 and SYNGAP1 genes. Information about the genetic influence on various diseases, including autism, in the Amerindian population from Amazon, is still scarce. We investigated 35 variants of the CHD8, SCN2A, FOXP1, and SYNGAP1 gene in Amazonian Amerindians in comparison with publicly available population frequencies from the 1000 Genomes Project database. Our study identified 16 variants in the Amerindian population of the Amazon with frequencies significantly different from the other populations. Among them, the SCN2A (rs17183814, rs75109281, and rs150453735), FOXP1 (rs56850311 and rs939845), and SYNGAP1 (rs9394145 and rs115441992) variants presented higher frequency than all other populations analyzed. In addition, nine variants were found with lower frequency among the Amerindians: CHD8 (rs35057134 and rs10467770), SCN2A (rs3769951, rs2304014, rs1838846, and rs7593568), FOXP1 (rs112773801 and rs56850311), and SYNGAP1 (rs453590). These data show the unique genetic profile of the indigenous population of the Brazilian Amazon. Knowledge of these variants can help to understand the pathophysiology and diagnosis of autism among Amerindians, Brazilians, and in admixed populations that have contributions from this ethnic group.

Life's simple 7 and all-cause mortality. A population-based prospective cohort study in middle-aged and older adults of Amerindian ancestry living in rural Ecuador.

Life's Simple 7 is an initiative of the American Heart Association developed for stratifying risk factors associated with adverse vascular outcomes and premature mortality. While this scale has been widely used, there is limited information on its applicability to individuals living in remote communities where risk factors and lifestyles differ from those found in urban settings. This longitudinal prospective study aimed to assess, according to the Life's Simple 7 scale, all-cause mortality in community-dwelling middle-age and older adults of Amerindian ancestry living in rural Ecuador. A total of 933 Atahualpa residents aged ≥ 40 years who received baseline interviews and procedures for measurement of cardiovascular health (CVH) metrics were enrolled and followed-up for a median of 8 years (interquartile range: 4-9 years). Using a Poisson regression model (adjusted for age at baseline, gender and the level of education), the predicted incidence rate of mortality was 4.22 per 100 person-years (95% C.I.: 2.48-5.97) for individuals with 0-1 CVH metrics in the ideal range, which decreased to 1.23 (95% C.I.: 0.24-2.21) for those with five ideal metrics. In an adjusted Cox-proportional hazard model that included all the CVH metrics, having three or more metrics in the ideal range significantly reduced the mortality hazard ratio when compared with individuals having 0-2 ideal metrics. Study results emphasize the usefulness of the Life's Simple 7 scale to estimate mortality risk in Amerindians living in remote communities. Control of CVH metrics should prove cost-effective for reducing premature deaths in underserved populations.

Height is Inversely Associated with Biomarkers of Intracranial Atherosclerotic Disease in Older Adults of Amerindian Ancestry: Exploring the Obesity Paradox.

BACKGROUND: Various anthropometric measurements have been inversely associated with atherosclerosis, giving rise to the concept of an "obesity paradox" However, inconsistent study results make it difficult to determine the best anthropometric measurement with which to assess such inverse relationship. Height has been inversely associated with atherosclerosis and it is unlikely to be associated with unexpected biases. In this study, we aimed to assess the association between height and other anthropometric measurements and intracranial atherosclerotic disease (ICAD). METHODS: Community-dwelling older adults enrolled in the Three Villages Study received anthropometric measurements, high-resolution head CT (to evaluate calcium content in carotid siphons) and time-of-flight MRA (to assess stenosis of large intracranial arteries). Logistic regression models were fitted to assess the independent association between each anthropometric measurements and the presence of ICAD, after adjusting for relevant confounders. Estimated adjusted proportions were used to show how increases of different anthropometric measurements impacted ICAD log odds and corresponding odds ratios. RESULTS: A total of 581 individuals were enrolled. Height was the single variable inversely associated with ICAD at the mean of other anthropometric measurements (OR: 0.954; 95% C.I.: 0.918 - 0.991; p=0.016). Every additional cm of height reduced by 4.6% the probability of having ICAD. The significance of other anthropometric measurements vanished in multivariate models with height as an independent variable. CONCLUSIONS: This study demonstrates a robust inverse association between height and ICAD in Amerindians and opens new avenues of research for a better understanding of the obesity paradox in diverse ethnic groups.

Variants of the Circle of Willis as seen on magnetic resonance angiography and carotid siphon calcifications in community-dwelling older adults.

BACKGROUND AND PURPOSE: Information on the association between anatomical variants of the Circle of Willis (CoW) and intracranial atherosclerotic disease (ICAD) is limited and results are controversial. In this population-based study, we aimed to assess whether an incomplete CoW is associated with high calcium content in carotid siphons (a reliable biomarker of ICAD) in community-dwelling older adults of Amerindian ancestry. METHODS: Individuals aged ≥60 years enrolled in the Three Villages Study received a head computed tomography (CT) and magnetic resonance angiogram (MRA) of intracranial vessels. The CoW was classified in complete or incomplete according to the presence or absence of one A1 segment of the anterior cerebral artery or one or both P1 segments of posterior cerebral arteries. Calcium content in carotid siphons was rated as low or high. A multivariate logistic model was fitted to assess the independent association between incompleteness of the CoW and high calcium content in carotid siphons, after adjusting for demographics and cardiovascular risk factors. RESULTS: A total of 581 individuals were enrolled (mean age: 71 ± 8.4 years; 57% women). MRA revealed an incomplete CoW in 227 (39%) individuals, and high-resolution CT disclosed high calcium content in carotid siphons in 185 (32%). A risk factor logistic regression model showed no independent association between incompleteness of the CoW and high calcium content in carotid siphons (odds ratio: 0.91; 95% confidence interval: 0.62-1.34; p = 0.631). CONCLUSION: Study results disclosed no association between anatomical variants of the CoW and the presence of high calcium content in carotid siphons.

Total Cerebral Small Vessel Disease Score and Anthropometric Indices: A Population-Based Study in Older Adults of Amerindian Ancestry.

A total of 590 older adults of Amerindian ancestry living in rural Ecuador received anthropometric measurements and a brain magnetic resonance imaging to estimate the total cerebral small vessel disease (cSVD) score. A fully adjusted ordinal logistic regression model, with categories of the total cSVD score as the dependent variable, disclosed significant associations between the waist circumference, the waist-to-hip, and the waist-to-height ratios - but not the body mass index (BMI) - and the cSVD burden. Indices of abdominal obesity may better correlate with severity of cSVD than the BMI in Amerindians. Phenotypic characteristics of this population may account for these results.

HLA-G in Mayas from Yucatan: An evolutionary approach.

HLA-G allele frequencies were studied in Yucatán (Mexico) Maya Amerindians by a direct exon DNA sequencing technique. It is described that Mayas are probably one of the first populations together with Olmecs that populated Meso America and that important HLA genetic differences between Mexican and Guatemalan Mayas support that Maya languages were imposed to several neighbouring Amerindian groups. HLA-G*01:01:02, HLA-G*01:01:01 and HLA-G*01:04:01 are the most frequent alleles in this population. It is remarkable that HLA-G*01:05N allele was not found in the population in accordance with similar results found in another Amerindians. Also, protein allele HLA-G*01:04 frequency is found not to differ to those found in another far or close living Amerindians in contrast to other World populations. It seems that while high HLA-G*01:05N frequency is found in Iran and Middle East populations, probably where this allele appeared within an ancestral HLA-A*19 group of alleles haplotype and it is maintained by unknown evolutionary forces, Amerindians do not have a high frequency because a founder effect or because required natural evolutionary forces do not exist in America. Finally, we believe useful to study HLA-G evolution for its physiopathology understanding in addition to the many papers on statistics on HLA-G and in vitro models that are yearly published.

Identification of New Helicobacter pylori Subpopulations in Native Americans and Mestizos From Peru.

Region-specific Helicobacter pylori subpopulations have been identified. It is proposed that the hspAmerind subpopulation is being displaced from the Americans by an hpEurope population following the conquest. Our study aimed to describe the genomes and methylomes of H. pylori isolates from distinct Peruvian communities: 23 strains collected from three groups of Native Americans (Asháninkas [ASHA, n = 9], Shimaas [SHIM, n = 5] from Amazonas, and Punos from the Andean highlands [PUNO, n = 9]) and 9 modern mestizos from Lima (LIM). Closed genomes and DNA modification calls were obtained using SMRT/PacBio sequencing. We performed evolutionary analyses and evaluated genomic/epigenomic differences among strain groups. We also evaluated human genome-wide data from 74 individuals from the selected Native communities (including the 23 H. pylori strains donors) to compare host and bacterial backgrounds. There were varying degrees of hspAmerind ancestry in all strains, ranging from 7% in LIM to 99% in SHIM. We identified three H. pylori subpopulations corresponding to each of the Native groups and a novel hspEuropePeru which evolved in the modern mestizos. The divergence of the indigenous H. pylori strains recapitulated the genetic structure of Native Americans. Phylogenetic profiling showed that Orthogroups in the indigenous strains seem to have evolved differentially toward epigenomic regulation and chromosome maintenance, whereas OGs in the modern mestizo (LIM) seem to have evolved toward virulence and adherence. The prevalence of cagA +/vacA s1i1m1 genotype was similar across populations (p = 0.32): 89% in ASHA, 67% in PUNO, 56% in LIM and 40% in SHIM. Both cagA and vacA sequences showed that LIM strains were genetically differentiated (p < 0.001) as compared to indigenous strains. We identified 642 R-M systems with 39% of the associated genes located in the core genome. We found 692 methylation motifs, including 254 population-specific sequences not previously described. In Peru, hspAmerind is not extinct, with traces found even in a heavily admixed mestizo population. Notably, our study identified three new hspAmerind subpopulations, one per Native group; and a new subpopulation among mestizos that we named hspEuropePeru. This subpopulation seems to have more virulence-related elements than hspAmerind. Purifying selection driven by variable host immune response may have shaped the evolution of Peruvian subpopulations, potentially impacting disease outcomes.

Assessment of Neck Grasp as a Screening Tool for Identifying Obstructive Sleep Apnea in Community-Dwelling Older Adults.

BACKGROUND: Inability to encircle the neck by hands (neck grasp) has been proposed as an indicator of obstructive sleep apnea (OSA) that would be useful for recognition of candidates for polysomnography (PSG). We assessed the value of neck grasp for predicting OSA in community-dwelling older adults of Amerindian ancestry. METHODS: Neck grasp was evaluated in individuals aged ≥60 years undergoing PSG. The association between neck grasp and OSA was assessed by logistic regression models adjusted for relevant covariates. Mediation analysis was used to establish the proportion of the effect of the association between neck grasp and OSA, which is mediated by the neck circumference (a well-known OSA biomarker). Receiver operator characteristics curve analysis was used to estimate diagnostic accuracy of neck grasp for predicting OSA. RESULTS: Of 201 individuals undergoing PSG, 167 (83%) had the neck grasp test. The remaining 34 could not perform the test because of different factors. Neck grasp was positive in 127 (76%) cases, and 114 (68%) individuals had OSA (apnea-hypopnea index ≥5). Multivariate logistic regression models disclosed a significant association between neck grasp and OSA. The neck circumference was the single covariate remaining independently significant in these models. Neck grasp was not efficient at predicting OSA (sensitivity: 83.3%, specificity: 39.6%, positive predictive value: 0.75 and negative predictive value: 0.53). The area under the curve disclosed only a moderate predictive capability (61.5%) of neck grasp. CONCLUSION: Results do not support the use of neck grasp as an independent predictor of OSA in the study population.

Prevalence and Correlates of Intracranial Atherosclerotic Disease Among Community-Dwelling Older Adults of Amerindian Ancestry. The Three Villages Study.

BACKGROUND: Knowledge on the prevalence and correlates of intracranial atherosclerotic disease (ICAD) is limited. We aimed to assess prevalence, clinical and neuroimaging correlates of ICAD in a cohort of older adults of Amerindian ancestry. METHODS: The study included 581 community-dwellers aged ≥60 years (mean age 71 ± 8.4 years; 57% women) living in rural Ecuadorian villages. ICAD was identified by means of CT determinations of carotid siphon calcifications (CSC) or MRA findings of significant stenosis of intracranial arteries. Fully-adjusted logistic regression models were fitted with biomarkers of ICAD as the dependent variables. RESULTS: A total of 205 (35%) of 581 participants had ICAD, including 185 with high calcium content in the carotid siphons and 40 with significant stenosis of at least one intracranial artery (20 subjects had both biomarkers). Increasing age, high fasting blood glucose, >10 enlarged basal ganglia-perivascular spaces and non-lacunar strokes were associated with high calcium content in the carotid siphons. In contrast, male gender, moderate-to-severe white matter hyperintensities, lacunar and non-lacunar strokes were associated with significant stenosis of intracranial arteries. Stroke was more common among subjects with any biomarker of ICAD than in those with no biomarkers (29% versus 9%, p < 0.001). Significant stenosis of intracranial arteries was more often associated with stroke than high calcium content in the carotid siphons, suggesting that CSC are more likely an ICAD biomarker than causally related to stroke. CONCLUSIONS: ICAD prevalence in Amerindians is high, and is significantly associated with stroke. CSC and significant stenosis of intracranial arteries may represent different phenotypes of ICAD.