Adopting a Precision Medicine Paradigm in Puerto Rico: leveraging ancestral diversity to identify predictors of clopidogrel response in Caribbean Hispanics
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PROVIDER: PRJNA948120 | ENA |
REPOSITORIES: ENA
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Project description:Adopting a Precision Medicine Paradigm in Puerto Rico: leveraging ancestral diversity to identify predictors of clopidogrel response in Caribbean Hispanics
| PRJNA948119 | ENA
Project description:Existing algorithms account for ~50% of observed variance in warfarin dose requirements after including common polymorphisms. However, they do not perform as well in populations other than Caucasians, in part because some ethno-specific genetic variants are overlooked. The objective of the present study was to identify genetic polymorphisms that can explain variability in warfarin dose requirements among Caribbean Hispanics of Puerto Rico. Next-Generation Sequencing of candidate genes CYP2C9 and VKORC1 and genotyping by DMET® Plus Assay of cardiovascular patients were performed. We also aimed at characterizing the genomic structure and admixture pattern of this study cohort. Our study used the Extreme Discordant Phenotype approach to perform a case-control association analysis. The CYP2C9 variant rs2860905, which was found in all the major haplotypes occurring in the Puerto Rican population, showed stronger association with warfarin sensitivity (<4 mg/day) than common variants CYP2C9*2 and CYP2C9*3. Although, CYP2C9*2 and CYP2C9*3 are separately contained within two of the haplotypes, 10 subjects with the sensitive phenotype were carriers of only the CYP2C9 rs2860905 variant. Other polymorphisms in CES2 and ABCB1 were found to be associated with warfarin resistance. Incorporation of rs2860905 in a regression model (R2 = 0.63, MSE = 0.37) that also includes additional genetics (i.e., VKORC1-1639 G>A; CYP2C9 rs1856908; ABCB1 c.IVS9-44A>G/ rs10276036; CES2 c.269-965A>G/ rs4783745) and non-genetic factors (i.e., hypertension, diabetes and age) showed better prediction of warfarin dose requirements than CYP2C9*2 and CYP2C9*3 combined (partial R2 = 0.132 vs. 0.023 and 0.007, respectively, p < 0.001). The genetic background of Puerto Ricans in the study cohort showed a tri-hybrid admixture pattern, with a slightly higher than expected contribution of Native American ancestry (25%). The genomic diversity of Puerto Ricans is highlighted by the presence of four different major haplotype blocks in the CYP2C9 locus. Although, our findings need further replication, this study contributes to the field by identifying novel genetic variants that increase predictability of stable warfarin dosing among Caribbean Hispanics.
| S-EPMC5461284 | biostudies-literature
Project description:Viral strains, age, and host factors including genetics and proteins are associated with variable immune responses against SARS-CoV-2 and disease severity. We hypothesized that unique proteins/pathways are associated with COVID-19 disease severity in Puerto Rican Hispanics. A total of 121 men and women aged 21-80 years-old were recruited in Puerto Rico. Plasma samples were collected from unvaccinated COVID-19 infected subjects during acute disease (n=39) and compared to COVID-19 negative individuals (n=56) during acute disease using proteomics and cytokine expression. Infected individuals were stratified based on symptomatology as follows: mild (n=18), moderate (n=13), and severe (n=8). Quantitative proteomics was performed in plasma samples using Tandem Mass Tag (TMT) labeling. Cytokines in plasma were quantified using a human cytokine array. Proteomics analyses revealed 56 differentially regulated proteins and the top 3 pathways that were predicted to be inhibited in severe patients including LXR/RXR signaling, Production of NO and ROS in macrophages, and Synaptogenesis signaling. Decreased cadherin-13 validated by ELISA, which participates in synaptogenesis, is a novel protein is a novel protein not previously reported in other studies of COVID-19 severity and validated by ELISA. Cytokine analyses showed that TNF⍺ levels decreased with disease severity. This study uncovers potential host predictors of COVID-19 severity and new avenues for treatment in Puerto Rican Hispanics.
2024-06-16 | PXD046103 | Pride
Project description:Colorectal cancer (CRC) is a leading cause of morbidity and mortality and alterations in mismatch repair (MMR) genes, leading to absent protein (negative) expression, are responsible for approximately 20% of CRC cases. Immunohistochemistry is a tool for prescreening of MMR protein expression in CRC but the literature on its use on Hispanics is scarce. However, Hispanics represent the second leading ethnicity in the United States (US) and CRC is a public health burden in this group. Our objectives were to determine the frequency of MMR protein-negative CRC and to evaluate its association with clinical and pathological characteristics among Hispanics from Puerto Rico, for the first time to our knowledge. A retrospective observational study of unselected CRC patients from the Puerto Rico Medical Center from 2001 to 2005 was done. MLH1 and MSH2, the most commonly altered MMR genes, protein expression was evaluated using immunohistochemistry, with microsatellite instability (MSI) and BRAF gene analyses in the absence of MLH1 protein expression. One-hundred sixty-four CRC patients were evaluated: the overall MMR protein-negative frequency was 4.3%, with 0.6% frequency of co-occurrence of MLH1-protein negative expression, MSI-high, and normal BRAF gene. MMR protein-negative expression was associated with proximal colon location (P = 0.02) and poor histological tumor differentiation (P = 0.001), but not with other characteristics. The frequency of MMR protein-negative CRC in Hispanics from Puerto Rico was lower than reported in other populations. This finding may explain the lower CRC incidence rate among US Hispanics as compared to US non-Hispanic whites and blacks.
| S-EPMC2873132 | biostudies-literature
Project description:The nearly 200 species of direct-developing frogs in the genus Eleutherodactylus (the Caribbean landfrogs, which include the coquís) comprise an important lineage for understanding the evolution and historical biogeography of the Caribbean. Time-calibrated molecular phylogenies provide indirect evidence for the processes that shaped the modern anuran fauna, but there is little direct evidence from the fossil record of Caribbean frogs about their distributions in the past. We report a distal humerus of a frog from the Oligocene (approx. 29 Ma) of Puerto Rico that represents the earliest known fossil frog from any Caribbean island. Based on its prominent rounded distal humeral head, distally projecting entepicondyle, and reduced ectepicondyle, we refer it to the genus Eleutherodactylus. This fossil provides additional support for an early arrival of some groups of terrestrial vertebrates to the Greater Antilles and corroborates previous estimates based on molecular phylogenies suggesting that this diverse Caribbean lineage was present in the islands by the mid-Cenozoic.
| S-EPMC7211465 | biostudies-literature
Project description:The cervicovaginal microbiota is influenced by host physiology, immunology, lifestyle, and ethnicity. We hypothesized that there would be differences in the cervicovaginal microbiota among pregnant, nonpregnant, and menopausal women living in Puerto Rico (PR) with and without human papillomavirus (HPV) infection and cervical cancer. We specifically wanted to determine if the microbiota is associated with variations in cervical cytology. A total of 294 women, including reproductive-age nonpregnant (N = 196), pregnant (N = 37), and menopausal (N = 61) women, were enrolled. The cervicovaginal bacteria were characterized by 16S rRNA amplicon sequencing, the HPV was genotyped with SPF10-LiPA, and cervical cytology was quantified. High-risk HPV (HR-HPV, 67.3%) was prevalent, including genotypes not covered by the 9vt HPV vaccine. Cervical lesions (34%) were also common. The cervical microbiota was dominated by Lactobacillus iners. Pregnant women in the second and third trimesters exhibited a decrease in diversity and abundance of microbes associated with bacterial vaginosis. Women in menopause had greater alpha diversity, a greater proportion of facultative and strictly anaerobic bacteria, and higher cervicovaginal pH than premenopausal women. Cervical lesions were associated with greater alpha diversity. However, no significant associations between the microbiota and HPV infection (HR or LR-HPV types) were found. The cervicovaginal microbiota of women living in Puerto Rican were either dominated by L. iners or diverse microbial communities regardless of a woman's physiological stage. We postulate that the microbiota and the high prevalence of HR-HPV increase the risk of cervical lesions among women living in PR. IMPORTANCE In the enclosed manuscript, we provide the first in-depth characterization of the cervicovaginal microbiota of Hispanic women living in Puerto Rico (PR), using a 16S rRNA approach, and include women of different physiological stages. Surprisingly we found that high-risk HPV was ubiquitous with a prevalence of 67.3%, including types not covered by the 9vt HPV vaccine. We also found highly diverse microbial communities across women groups-with a reduction in pregnant women, but dominated by nonoptimal Lactobacillus iners. Additionally, we found vaginosis-associated bacteria as Dialister spp., Gardnerella spp., Clostridium, or Prevotella among most women. We believe this is a relevant and timely article expanding knowledge on the cervicovaginal microbiome of PR women, where we postulate that these highly diverse communities are conducive to cervical disease.
| S-EPMC10469956 | biostudies-literature
Project description:A Genomic Approach to Warfarin Dose Prescription in Admixed Caribbean Hispanics
| PRJNA421230 | ENA
Project description:A Genomic Approach to Warfarin Dose Prescription in Admixed Caribbean Hispanics
| PRJNA421231 | ENA
Project description:Women in the U.S. Commonwealth of Puerto Rico (PR) have a higher age-adjusted incidence rate for uterine cervix cancer than the U.S. mainland as well as substantial access and economic barriers to cancer care. The National Cancer Institute (NCI) funds a Minority/Underserved NCI Community Oncology Research Program in PR (PRNCORP) as part of a national network of community-based health-care systems to conduct multisite cancer clinical trials in diverse populations. Participation by the PRNCORP in NCI's uterine cervix cancer clinical trials, however, has remained limited. This study reports on the findings of an NCI site visit in PR to assess barriers impeding site activation and accrual to its sponsored gynecologic cancer clinical trials. Qualitative, semi-structured individual, and group interviews were conducted at six PRNCORP-affiliated locations to ascertain: long-term trial accrual objectives; key stakeholders in PR that address uterine cervix cancer care; key challenges or barriers to activating and to enrolling patients in NCI uterine cervix cancer treatment trials; and resources, policies, or procedures in place or needed on the island to support NCI-sponsored clinical trials. An NCI-sponsored uterine cervix cancer radiation-chemotherapy intervention clinical trial (NCT02466971), already activated on the island, served as a test case to identify relevant patient accrual and site barriers. The site visit identified five key barriers to accrual: (1) lack of central personnel to coordinate referrals for treatment plans, medical tests, and medical imaging across the island's clinical trial access points; (2) patient insurance coverage; (3) lack of a coordinated brachytherapy schedule at San Juan-centric service providers; (4) limited credentialed radiotherapy machines island-wide; and (5) too few radiology medical physicists tasked to credential trial-specified positron emission tomography scanners island-wide. PR offers a unique opportunity to study overarching and tactical strategies for improving accrual to NCI-sponsored gynecologic cancer clinical trials. Interview findings support adding and re-tasking personnel for coordinated trial-eligible patient referral, accrual, and treatment.
| S-EPMC5902541 | biostudies-literature