The frequency of rs2231142 in ABCG2 among Native Hawaiian and Pacific Islander subgroups: implications for personalized rosuvastatin dosing.
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ABSTRACT:
SUBMITTER: AlAzzeh O
PROVIDER: S-EPMC10072122 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
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The frequency of rs2231142 in <i>ABCG2</i> among Native Hawaiian and Pacific Islander subgroups: implications for personalized rosuvastatin dosing.
AlAzzeh Ola O Roman Youssef M YM
Pharmacogenomics 20230120 3
Statins are among the most commonly prescribed medications worldwide. Rosuvastatin is a moderate- to high-intensity statin depending on the prescribed dose. Statin-associated muscle symptoms are the main side effects, contributing to low adherence to statins. The missense variant rs2231142 in <i>ABCG2</i> affects the functionality of the ABCG2 transporter, altering the pharmacokinetics and pharmacodynamics of rosuvastatin. This special report aims to accentuate the importance of considering the ...[more]
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Project description:Statins are widely used medications for the primary and secondary prevention of cardiovascular diseases. Statin-induced musculoskeletal symptoms are the primary adverse drug events contributing to poor adherence to lipid-lowering therapy. Rosuvastatin is characterized by interindividual differences in systemic exposure among different patient population subgroups. The missense variant Q141K within ABCG2, highly prevalent in some Asian subgroups, results in decreased transporter efflux function and increased exposure to rosuvastatin. We aim to highlight the implications of ABCG2 genotype in prescribing rosuvastatin and the ramifications of interpopulation differences in Q141K frequencies in the starting dose of rosuvastatin in major Asian subgroups, using the most recent genetic-based guidelines. The high frequency of Q141K in Filipinos could warrant a lower starting rosuvastatin dose versus non-Filipinos. The Q141K genotype frequencies in Asian subgroups suggest significant interpopulation differences, reinforcing the need to move beyond race-based to genotype-based rosuvastatin dosing.
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Project description:Aim: Prevalence of clinically actionable genetic variants of CYP2C19 is lacking in specific population subgroups. This study aims to assess the frequencies of CYP2C19*2, *3, and *17 in Asian, Native Hawaiian and Pacific Islander (NHPI) population subgroups compared with Europeans. Patients & methods: The study included repository DNA samples of 1064 women, 18 years or older, who self-reported as Filipino, Korean, Japanese, Native Hawaiian, Marshallese and Samoan. Results: The overall frequencies of CYP2C19*2 (25-36%) and CYP2C19*3 (2.5-10%) were significantly higher in all our subgroups than in Europeans (15 and 0.02%, respectively). The overall frequency of CYP2C19*17 was significantly lower in all our subgroups (1-6%) than in Europeans (21.7%). Conclusion: This is the first report on the frequencies of CYP2C19*2, *3, and *17 in women of Asian and NHPI descent with distinct population subgroup differences. Differential allele frequencies of CYP2C19 among population subgroups underscore the importance of increasing racial and ethnic diversity in pharmacogenetic research.
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Project description:ImportanceHaving diverse participants in clinical trials ensures new drug products work well across different demographic groups, making health care safer and more effective for everyone. Information on the extent of Native Hawaiian and Pacific Islander participation in clinical trials is limited.ObjectiveTo examine representation of Native Hawaiian and Pacific Islanders in clinical trials leading to the first US Food and Drug Administration (FDA) approvals for the 10 drug products with the top worldwide sales forecasts in 2024.Design, setting, and participantsCross-sectional secondary analysis of existing data from clinical trials that took place from 2006 to 2021 in the US. All clinical trials that were included in the FDA first approval application for the 10 drug products were evaluated in this study. Data were analyzed from February to August 2024.ExposureParticipation in a clinical drug trial.Main outcomes and measuresComparison of the proportion of Native Hawaiian and Pacific Islander participation in clinical trials for the 10 drug products with top sales forecasts in 2024 to the Native Hawaiian and Pacific Islander population proportion.ResultsIn this cross-sectional study of 139 062 individuals, Native Hawaiian and Pacific Islander participation in clinical trials for the 10 drug products with top sales forecasts was either unknown or low. For 6 of the 10 drug products (60%), the number of Native Hawaiian and Pacific Islander participants was not documented. All trials that reported Native Hawaiian and Pacific Islander participation had fewer Native Hawaiian and Pacific Islander participants than would be expected based on their US population proportion, with 2 of the differences being statistically significant. Of the trials that disaggregated Native Hawaiian and Pacific Islander participants from other racial groups, the number of Native Hawaiian and Pacific Islander participants was 8 for risankizumab-rzaa (0.38% of participants vs 0.49% of the population; percentage point difference, -0.11%; 95% CI, -0.37% to -0.15%), 7 for bictegravir/emtricitabine/tenofovir alafenamide (0.38% of participants vs 0.49% of the population; percentage point difference, -0.10%; 95% CI, -0.39% to 0.18%), 27 for 4vHPV/9vHPV (0.15% of participants vs 0.46% of the population; percentage point difference, -0.31%; 95% CI, -0.37% to -0.26%), and 90 for BNT162B2 COVID-19 vaccine (0.20% of participants vs 0.52% of the population; percentage point difference, -0.32; 95% CI, -0.36% to -0.27%).Conclusions and relevanceIn this cross-sectional study, limited documentation and participation of Native Hawaiian and Pacific Islander individuals in clinical trials for drug products with top sales forecasts was found. This is especially concerning because Native Hawaiian and Pacific Islander individuals have a higher risk than other racial groups for type 2 diabetes, cancer, and several other conditions the products examined in this study treat. Given the importance of enrolling Native Hawaiian and Pacific Islander participants in clinical trials, sites should be established in key geographic regions, such as Hawai'i, and postmarket studies should be conducted within Native Hawaiian and Pacific Islander populations.
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Project description:BackgroundGout, an inflammatory condition, is characterized by the precipitation of monosodium urate crystals (MSU) in or around distal joints. The latter is caused by chronic hyperuricemia (HU)-high urate levels in the blood. Genetic variations in urate transporters play a significant role in determining urate levels within the human body, rendering some racial and ethnic groups more or less susceptible to developing either HU or gout. This study aims to estimate the frequencies of HU and gout risk alleles in Asian, Native Hawaiian, and Pacific Islander subgroups, using biorepository DNA samples.MethodsThe biospecimens repository at the University of Hawai'i provided DNA samples of consented post-partum women of Japanese, Filipino, Korean, Native Hawaiian, Samoan, and Marshallese descent. The DNA was previously extracted from maternal blood and genotyped at the Genomics and Bioinformatics Shared Resource, Cancer Center (Honolulu, HI). Nine urate genes: ABCG2, SLC2A9, SLC16A9, GCKR, SLC22A11, SLC22A12, LRR16A, PDZK1, and SLC17A1, were selected due to their significant association with HU and gout risk. Hardy-Weinberg Equilibrium (HWE) for genotype frequencies was assessed, using the Chi-Square test with p < 0.006 for statistical significance. Allele frequencies in our study were then compared to EUR from the 1000 Genomes Project Database Phase III, using Chi-square or Fisher's exact test, when appropriate. Bonferroni correction for multiple comparisons was used, with p < 0.006 for statistical significance.ResultsOur study involved 1059 post-partum women 18-year-old or older who self-reported their respective race and ethnicity, including Asian, Native Hawaiian, and Pacific Islander ancestry. The Asian subgroups included Japanese, Filipino, and Korean. The Pacific Islander subgroups included Marshallese and Samoan. None of the study participants had a history of gout. We excluded the PDZK1 gene from the final analysis due to its deviation from HWE (p < 0.006) across all the population subgroups, with eight loci remaining for cross-subgroup comparisons. Compared to EUR, the genetic polymorphism frequencies were significantly different-8/8 in Japanese, 6/8 in Korean, 6/8 in Filipino, 8/8 in Samoan, 6/8 in Native Hawaiian, and 6/8 in Marshallese. HU and gout risk alleles indices were 8, 6, 5, 5, 4, and 4 in Japanese, Filipino, Korean, Samoan, Marshallese, and Native Hawaiian, respectively. The percentage of cumulative risk alleles was 100% in both Japanese and Filipino, followed by 83.5% in Korean.ConclusionsCompared to EUR, Asian subgroups, particularly Japanese, Filipino, and Korean, had the highest percentage of the cumulative uric acid risk alleles. These results could partly explain the increased risk of developing gout among some Asian ancestral subgroups compared to EUR.
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Project description:BackgroundThe risk of diabetes among Asian, Native Hawaiian, and Pacific Islander (ANHPI) women after breast cancer is unclear. This study estimated the risk of incident type II diabetes in older ANHPI and older non-Hispanic White (NHW) women with breast cancer from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Medicare linked claims.MethodsA matched cohort of 7122 older ANHPI and 21 365 older NHW women with breast cancer were identified from SEER-Medicare between 2000 and 2017. To assess the risk of incident type II diabetes after breast cancer, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated using the Cox proportional-hazards regression model.ResultsDuring the mean 8 years of follow-up, 9.3% of older women with breast cancer developed incident type II diabetes. In comparison with older NHW women, older ANHPI women without a known history of diabetes had an elevated risk of diabetes after breast cancer, with strong associations observed for Pacific Islander (HR = 3.09, 95% CI = 1.43 to 6.67), Vietnamese (HR = 2.12, 95% CI = 1.33 to 2.36), and Filipino (HR = 2.02, 95% CI = 1.57 to 2.59) women with breast cancer, adjusting for potential confounders. Among ANHPI women with breast cancer, more baseline comorbidities and obesity were risk factors for developing incident type II diabetes.ConclusionANHPI women diagnosed with breast cancer had an elevated risk of type II diabetes compared with older NHW women with breast cancer. Routine monitoring and management of diabetes are warranted in older ANHPI women with breast cancer.
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Project description:This study examined differences in poverty and health among Native Hawaiians and Pacific Islanders (NHPI) and 6 disaggregated Asian ethnic subgroups and an aggregated Other Asian category. Participants were followed longitudinally for 2 years using data from 2009 to 2019 from the Current Population Survey, a monthly survey conducted by the Census Bureau. Having 2 years of data enabled the study to assess both prevalence of poverty and fair/poor health in only 1 of the 2 years and in both years. For NHPI, 13.5% were in poverty 1of the 2 years and 7.1% in both years. Asian ethnicities showed high variability ranging from a low of 6.4% for 1 year and 1.9% for 2 years among Asian Indians to 16.0% for 1 year and 6.3% for 2 years among Vietnamese. Fair/poor health also showed ethnic variability, made most apparent after age-sex adjustment in regression models. For poverty, after adjustment, Asian Indians, Filipinos and Japanese had significantly lower odds of being in poverty at least 1 year than NHPI. For having fair/poor health, Asian Indians and Japanese experienced lower odds than NHPI for both 1 and 2 years and Filipinos for 1 year, after age/sex adjustment. The results emphasize the diversity of Asian and Pacific Islander populations, the variability of poverty over time, and the importance of using disaggregated data to understand ethnic differences in poverty and health. These findings can be used to inform future modeling of social determinants on poverty and health among NHPI and Asian subgroups.
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Project description:BackgroundIn recent years, tuberculosis (TB) incidence in the United States has declined overall but remained high among Native Hawaiian and Other Pacific Islander (NH/PI) persons. Few studies have examined the epidemiology of TB among NH/PI persons, particularly in the U.S.-Affiliated Pacific Islands (USAPI). We describe TB incidence and characteristics of NH/PI patients during 2010-2019.MethodsWe used data from the National Tuberculosis Surveillance System to characterize TB cases reported among NH/PI persons born in the 50 U.S. states (defined to include District of Columbia) and the USAPI. We calculated annual TB incidence among NH/PI patients, stratified by place of birth (U.S. states or USAPI). Using Asian persons born outside the United States-persons historically grouped with NH/PI persons as one racial category-as the reference, we compared demographic, clinical, and socio-behavioral characteristics of NH/PI TB patients.ResultsDuring 2010-2019, 4359 TB cases were reported among NH/PI patients born in the U.S. states (n=205) or the USAPI (n=4154). Median annual incidence per 100,000 persons was 6.5 cases (persons born in the U.S. states) and 150.7 cases (persons born in the USAPI). The proportion of TB patients aged <15 years was higher among NH/PI persons (U.S. states: 54%, USAPI: 24%) than among Asian persons born outside the United States (1%).ConclusionsTB incidence among NH/PI persons is high, particularly among persons born in the USAPI, emphasizing the need to enhance TB prevention strategies in these communities. Interventions should be tailored toward those who experience the highest risk, including NH/PI children and adolescents.
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Project description:ImportanceSuicide is one of the leading causes of death for Asian American, Native Hawaiian, and Pacific Islander adolescents, but because these individuals are analyzed in aggregate, potentially important differences in suicide risk are obscured.ObjectiveTo disaggregate Asian and Native Hawaiian or Pacific Islander adolescents into racial and ethnic subgroups and compare risks of suicidal ideation between and within the subgroups.Design, setting, and participantsThis cross-sectional study used pooled data from 4-year public high school students (9th and 11th grade) participating in the 2017-2018 and 2018-2019 California Healthy Kids Survey. Data were analyzed between January 5, 2023, and March 31, 2024.ExposuresSelf-reported race and ethnicity, including American Indian or Alaska Native, Asian, Black, Hispanic or Latinx, Native Hawaiian or Pacific Islander, and White, and 9 Asian and Native Hawaiian or Pacific Islander subgroups, including Asian Indian, Chinese, Filipino, Japanese, Korean, Native Hawaiian or Pacific Islander, other Asian, Southeast Asian (ie, Cambodian, Hmong, Laotian), and Vietnamese.Main outcome and measuresPast-year suicidal ideation was the primary outcome. Analyses compared an aggregated Asian and Native Hawaiian or Pacific Islander group with subgroups disaggregated by ethnicity and by monoethnic or monoracial, multiethnic, and multiracial identifications. Logistic regression models were used to test between- and within-group differences.ResultsAmong 547 816 California adolescents in 9th or 11th grade surveyed (50.3% girls), 77 735 (14.2%) identified as Asian or Native Hawaiian or Pacific Islander. The prevalence of suicidal ideation was 17.5% (95% CI, 17.1%-17.9%) among adolescents in the combined Asian and Native Hawaiian or Pacific Islander group. After disaggregation into subgroups, prevalence of suicidal ideation ranged from 13.3% (95% CI, 12.3%-14.4%) for monoethnic Asian Indian adolescents to 21.2% (95% CI, 20.4%-21.9%) for monoethnic Filipino adolescents. Multiethnic and multiracial identity was associated with elevated risk of suicidal ideation for all groups, from 2.3 percentage points (from 21.2% [95% CI, 20.4%-21.9%] among monoethnic to 23.5% [95% CI, 22.8%-24.2%] among multiracial Filipino adolescents) to 9.4 percentage points (from 13.7%, [95% CI, 13.0%-14.4%] among monoethnic to 23.1% [95% CI, 22.1%-24.1%] among multiracial Chinese adolescents). Compared with a mutually exclusive approach, an additive model allowing for self-report of multiple identities had the best fit and showed a higher prevalence of suicidal ideation among multiethnic and multiracial Asian and Native Hawaiian or Pacific Islander adolescents compared with monoethnic Chinese adolescents.Conclusions and relevanceThe results from this cross-sectional study provide evidence for disaggregation of heterogeneous ethnoracialized groups as a data equity strategy that may illuminate hidden disparities in adolescent suicidal ideation risk. Further research is imperative to understand suicide risk among Asian, Native Hawaiian, and Pacific Islander adolescents who identify with multiple ethnic or racial groups.
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Project description:BackgroundCardiotoxicity among breast cancer survivors is associated with chemotherapy and radiation therapy. The risk of cardiovascular disease (CVD) among Asian, Native Hawaiian and Pacific Islander (ANHPI) breast cancer survivors in the United States is unknown.MethodsWe used the SEER-Medicare linked database to estimate the risk of CVD among older breast cancer survivors. International Classification of Disease diagnosis codes were used to identify incident CVD outcomes. Cox proportional hazards models were used to estimate HRs and 95% confidence intervals (CI) comparing ANHPI with Non-Hispanic White (NHW) patients with breast cancer for CVD, and among ANHPI race and ethnicity groups.ResultsA total of 7,122 ANHPI breast cancer survivors and 21,365 NHW breast cancer survivors were identified. The risks of incident heart failure and ischemic heart disease were lower among ANHPI compared with NHW breast cancer survivors (HRheart failure, 0.72; 95% CI, 0.61-0.84; HRheart disease, 0.74; 95% CI, 0.63-0.88). Compared with Japanese patients with breast cancer, Filipino, Asian Indian and Pakistani, and Native Hawaiian breast cancer survivors had higher risks of heart failure. ischemic heart disease and death. Among ANHPI breast cancer survivors, risk factors for heart failure included older age, higher comorbidity score, distant cancer stage and chemotherapy.ConclusionsOur results support heterogeneity in CVD outcomes among breast cancer survivors among ANHPI race and ethnicity groups. Further research is needed to elucidate the disparities experienced among ANHPI breast cancer survivors.ImpactFilipino, Asian Indian and Pakistani, and Native Hawaiian patients with breast cancer had higher risks of heart failure, ischemic heart disease and death among ANHPI patients with breast cancer.
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