Dataset Information

Warfarin Anticoagulation Therapy in Caribbean Hispanics of Puerto Rico: A Candidate Gene Association Study.

ABSTRACT: 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.

SUBMITTER: Claudio-Campos K

PROVIDER: S-EPMC5461284 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Warfarin Anticoagulation Therapy in Caribbean Hispanics of Puerto Rico: A Candidate Gene Association Study.

Claudio-Campos Karla K Labastida Aurora A Ramos Alga A Gaedigk Andrea A Renta-Torres Jessicca J Padilla Dariana D Rivera-Miranda Giselle G Scott Stuart A SA Ruaño Gualberto G Cadilla Carmen L CL Duconge-Soler Jorge J

Frontiers in pharmacology 20170607

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 <i>CYP2C9< ...[more]

PMID: 28638342

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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.

Dataset Information

Warfarin Anticoagulation Therapy in Caribbean Hispanics of Puerto Rico: A Candidate Gene Association Study.

Publications

Warfarin Anticoagulation Therapy in Caribbean Hispanics of Puerto Rico: A Candidate Gene Association Study.

Similar Datasets

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