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CYP2C19 Polymorphisms in Indonesia: Comparison among Ethnicities and the Association with Clinical Outcomes.

ABSTRACT: CYP2C19 polymorphisms are important factors for proton pump inhibitor-based therapy. We examined the CYP2C19 genotypes and analyzed the distribution among ethnicities and clinical outcomes in Indonesia. We employed the polymerase chain reaction-restriction fragment length polymorphism method to determine the CYP2C19 genotypes and evaluated inflammation severity with the updated Sydney system. For CYP2C19*2, 46.4% were the homozygous wild-type allele, 14.5% were the homozygous mutated allele, and 39.2% were the heterozygous allele. For CYP2C19*3, 88.6% were the homozygous wild-type allele, 2.4% were the homozygous mutated allele, and 9.0% were the heterozygous allele. Overall, the prevalence of rapid, intermediate, and poor metabolizers in Indonesia was 38.5, 41.6, and 19.9%, respectively. In the poor metabolizer group, the frequency of allele *2 (78.8%) was higher than the frequency of allele *3 (21.2%). The Papuan had a significantly higher likelihood of possessing poor metabolizers than the Balinese (OR 11.0; P = 0.002). The prevalence of poor metabolizers was lower compared with the rapid and intermediate metabolizers among patients with gastritis and gastroesophageal reflux disease. Intermediate metabolizers had the highest prevalence, followed by rapid metabolizers and poor metabolizers. Dosage adjustment should therefore be considered when administering proton pump inhibitor-based therapy in Indonesia.

SUBMITTER: Miftahussurur M

PROVIDER: S-EPMC8067412 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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CYP2C19 Polymorphisms in Indonesia: Comparison among Ethnicities and the Association with Clinical Outcomes.

Miftahussurur Muhammad M Doohan Dalla D Syam Ari Fahrial AF Nusi Iswan Abbas IA Subsomwong Phawinee P Waskito Langgeng Agung LA Maulahela Hasan H Akil Fardah F Uwan Willy Brodus WB Siregar Gontar G Fauzia Kartika Afrida KA Rezkitha Yudith Annisa Ayu YAA Rahman Abdul A Wibawa I Dewa Nyoman IDN Saudale Alexander Michael Joseph AMJ Richardo Marselino M Sugihartono Titong T Chomariyati Alvi A Bramantoro Taufan T Uchida Tomohisa T Yamaoka Yoshio Y

Biology 20210406 4

CYP2C19 polymorphisms are important factors for proton pump inhibitor-based therapy. We examined the CYP2C19 genotypes and analyzed the distribution among ethnicities and clinical outcomes in Indonesia. We employed the polymerase chain reaction-restriction fragment length polymorphism method to determine the CYP2C19 genotypes and evaluated inflammation severity with the updated Sydney system. For CYP2C19*2, 46.4% were the homozygous wild-type allele, 14.5% were the ho ...[more]

PMID: 33917299

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Project description:ObjectivesThis study sought to evaluate the influence of the genetic polymorphisms on platelet reactivity and clinical outcomes in acute ischemic stroke patients taking clopidogrel.BackgroundLittle research has been published on relationships between genetic polymorphisms, platelet reactivity, and clinical outcomes in stroke patients treated with clopidogrel.MethodsPatients hospitalized in Changhai Hospital with acute ischemic stroke were randomly enrolled into treatment with a 75-mg daily maintenance dose of clopidogrel. Genotyping was detected by the MassARRAY iPLEX genotyping system (Sequenom Inc, San Diego, CA), and platelet reactivity was evaluated by the VerifyNow P2Y12 test (Accumetrics Inc., San Diego, CA). Sixteen single nucleotide polymorphisms (SNPs) within 9 genes were selected and high on-clopidogrel platelet reactivity (HPR) was defined as P2Y12 reaction units (PRU) value ≥230. The primary endpoint was ischemic events, including major adverse cardiac events (MACE), recurrence of stroke, transient ischemic attack (TIA), and the composite of vascular death, and the secondary endpoint was bleeding.ResultsOf the 345 patients recruited, 275 (79.7%) patients were followed up for 1 year and 122 (35.4%) patients were categorized as HPR. Among the SNPs selected, only the CYP2C19*2 allele and the CYP2C19*3 allele were statistically significantly associated with PRU (P < 0.001 and P = 0.003, respectively). Similarly, the prevalence of HPR was associated with CYP2C19*2 and CYP2C19*3 (P < 0.001 and P = 0.001, respectively). During the 1 year of follow-up, a total of 64 (23.3%) cases of clinical events occurred, including 60 ischemic events and 4 bleeding events. There were no correlation between CYP2C19 variant alleles and clinical outcomes (P > 0.05), but a statistically significant relevance was found between the HPR and the ischemic events in 1 year of follow-up (P = 0.001).ConclusionsCYP2C19*2 and CYP2C19*3 had a significant impact on clopidogrel response, but was not associated with ischemic events during 1 year of follow-up in patients with acute ischemic stroke. HPR was an independent risk factor for ischemic events, and the VerifyNow P2Y12 test may be available to guide individualized antiplatelet therapies in stroke patients in China.

Project description:The contribution of human genes to the variability of disease outcomes has been shown to be important across infectious diseases. Studies have shown mutations within specific human genes are associated with variable COVID-19 outcomes. We focused on the SARS-CoV-2 receptors/co-receptors to identify the role of specific polymorphisms within ACE2, TMPRSS2, NRP1 and CD147. Polymorphisms within ACE2 (rs2285666), TMPRSS2 (rs12329760), CD147 (rs8259) and NRP1 (rs10080) have been shown to associate with COVID-19 severity. Using cryopreserved samples from COVID-19-positive African, European and South Asian individuals within South Africa, we determined genotype frequencies. The genetic variant rs2285666 was associated with COVID-19 severity with an ethnic bias. African individuals with a CC genotype demonstrate more severe COVID-19 outcomes (OR = 7.5; 95% CI 1.164-80.89; p = 0.024) compared with those with a TT genotype. The expressions of ACE2 and SARS-CoV-2 viral load were measured using droplet digital PCR. Our results demonstrate rs2285666 and rs10080 were significantly associated with increased SARS-CoV-2 viral load and worse outcomes in certain ethnicities. This study demonstrates two important findings. Firstly, SARS-CoV-2 viral load is significantly lower in Africans compared with individuals of European and South Asian descent (p = 0.0002 and p < 0.0001). Secondly, SARS-CoV-2 viral load associates with specific SARS-CoV-2 receptor variants. A limited number of studies have examined the receptor/co-receptor genes within Africa. This study investigated genetic variants within the SARS-CoV-2 receptor/co-receptor genes and their association with COVID-19 severity and SARS-CoV-2 viral load across different ethnicities. We provide a genetic basis for differences in COVID-19 severity across ethnic groups in South Africa, further highlighting the importance of further investigation to determine potential therapeutic targets and to guide vaccination strategies that may prioritize specific genotypes.

Project description:ObjectiveThe outcomes of sepsis and septic shock patients are heterogonous, with avariable response despite standardized care. The aim of this study was toexplore the racial differences in septic shock outcomes, and theirassociation with genetic polymorphisms and cytokine levels in an Asianpopulation.Materials and methodsThis was an observational cohort study with Intensive Care units of a 500bedded tertiary care hospital in Singapore. 198 patients (73 Chinese, 73Malay and 52 Indian and others) admitted to the Khoo Teck Puat HospitalIntensive Care Unit between August 2016 and June 2017, with a diagnosis ofsevere sepsis (according to) were enrolled. Plasma interlukin-6 (IL-6),interlukin-10 (IL-10) and tumour necrosis factor-a (TNFa) were measuredusing a highly sensitive quantitative sandwich enzyme-linked immunosorbentassay (ELISA) (BioVendor, Modrice, Czech Republic). The gene panel studiedincluded 16 genes.ResultsThe rs7038903 common variant in SVEP1 gene showed significant associationwith sepsis severity independent of other variants in ordinal logistic andlinear regression model (p = 0.001 and p = 0.002 respectively). Moreover, the association between rs7038903 and increased hazard for death remained significant after further adjusting for cytokines level. Interestingly, significant differences were seen in plasma IL6 inindividuals with or without rs7038903 C allele (28pg/ml (IQR 12-86) vs90pg/ml (IQR 49-155); P=0.022) in patients with severe sepsis in the Malayethnic group.ConclusionOur study shows a promising polymorphism in SVEP1 gene (rs7038903) which isassociated with sepsis shock and 28 days mortality, independent of age, gender, and method of diagnosis and SOFA score. Collectively, while our findings so far have shown the additional value or measuring cytokines andgenetic markers in sepsis outcomes in the local population, further largescare studies are needed in a heterogeneous septic population with arigorous analysis to know the significance of our findings.How to cite this articleSiddiqui S, Gurung RL et al. Genetic Polymorphisms and Cytokine Profile of Different Ethnicities in Septic Shock Patients, and their Association with Mortality. Indian J Crit Care Med 2019;29(3):135-138.

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CYP2C19 Polymorphisms in Indonesia: Comparison among Ethnicities and the Association with Clinical Outcomes.

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<i>CYP2C19</i> Polymorphisms in Indonesia: Comparison among Ethnicities and the Association with Clinical Outcomes.

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