Search Results (36)

Background/Objectives: Alloantigen H is one of thirteen systems in the chicken. Little is known about this system which has two serological alleles. The objectives of this study were (1) to identify the genetic region encoding the chicken alloantigen H, and (2) to develop DNA detection-based methods to aid H system allele identification. Methods: SNP genotypes from Axiom chicken SNP arrays were established for samples with known H system serological types. Sources of DNA included two elite Hy-Line White Leghorn lines segregating for alloantigen H, non-pedigreed samples from the Northern Illinois University (NIU) DNA bank, plus inbred line samples. Sequence information was also available for the commercial and inbred lines. Results: GWAS results from the elite Hy-Line lines and NIU DNA bank samples showed a very strong peak in the same 4.20–4.30 Mbp region on chromosome 24. Predicted cell membrane expression and the presence of non-synonymous SNP were criteria to identify candidate genes. Seven genes in this region have membrane-associated products: MCAM (CD146), THY1, MFRP, CLDN25, KCNJ14L, ABCG4, and PDZD3. However, only MCAM had an SNP variation that matched the serological haplotypes. Lines known to be segregating for the H system had concordance rates between serological results and SNP haplotype of 95% for both the elite HYL lines and 99% for the NIU samples, indicating that the MCAM (CD146) gene encodes the chicken H blood system. Conclusions: The gene product is a cell adhesion molecule affecting multiple activities including angiogenesis, development, cell differentiation, cell migration, signaling transduction, and immune responses. Long, short, and soluble isoforms are found in chickens. The described DNA-based typing methods facilitate future investigations to examine H haplotype frequencies in lines with identified differential responses such as growth or immune responses. Determining H haplotype association with egg production, feed conversion, and other traits with economic importance will aid in determining the significance of this immune-related gene in overall poultry health. Full article

Background: This longitudinal study assessed the Uric Acid/HDL-Cholesterol (UA/HDL-C) ratio as a prognostic biomarker for fatty liver disease (FLD) during a five-year follow-up of 1022 participants from the Genetics of Atherosclerotic Disease (GEA) Study. FLD is a multifactorial disease associated with cardiometabolic comorbidities, and genetic variants affecting uric acid transport (ABCG2 rs2231142) and hepatic lipid metabolism (PNPLA3 rs738409). Early diagnosis is essential to prevent disease progression; however, standard diagnostics are expensive and not widely accessible, highlighting the need for noninvasive tools. Objectives: The study aimed to validate the UA/HDL-C as a long-term predictor for FLD and its effectiveness in risk stratification, including adjustment for cardiometabolic factors and genetics. Methods: Non-contrast computed tomography was used to diagnose FLD and rs738409 and rs2231142 were genotyped by real-time PCR. ROC curves, Kaplan–Meier survival analysis, and logistic regression were used. Results: The findings show that FLD patients exhibited significantly higher UA/HDL-C than controls at both baseline and follow-up (p < 0.0001). Higher UA/HDL-C quartiles were associated with greater FLD prevalence, exceeding 50% in the highest quartile. The index cut-off points were 0.18 in men and 0.09 in women. ROC analysis showed significant discrimination for FLD (AUC: 0.637 overall, 0.650 in men, 0.626 in women). Conclusions: Logistic regression confirmed a strong independent association between UA/HDL-C and FLD over five years, even after adjustment for genetic, biochemical, and anthropometric factors, OR = 3.53, 95% CI: 2.39–4.68, p < 0.0001. Results suggest this ratio could be an alternative to find and follow FLD early on, especially in places with few resources. Full article

Background: Pharmacogenetic markers associated with the need to switch patients from methotrexate (MTX) to biologic agents in moderate-to-severe psoriasis remain insufficiently studied. The pharmacokinetics of MTX depend on the individual characteristics of the patient, as well as on the function of specific transporters and enzymes involved in its absorption, distribution, metabolism, and elimination; therefore, polymorphisms in genes encoding these proteins may be considered pharmacogenetic predictors of MTX intolerance or insufficient efficacy. This study aimed to investigate genetic variants associated with MTX intolerance or insufficient efficacy leading to therapy switch. Methods: A total of 80 patients with moderate-to-severe psoriasis were included: 43 who required switching from MTX to biologics and 37 who continued MTX therapy. Twelve polymorphisms in transporter and metabolism-related genes (ABCB1 (rs1045642), MTHFR (rs1801133), ABCB1 (rs1128503), ABCC2 (rs3740066), ABCC2 (rs717620), ABCG2 (rs2231137), GSTP1 (rs1695), SLC19A1 (rs1051266), COL18A1 (rs9977268), SLCO1B1 (rs2306283), SLCO1B1 (rs4149056), and ABCB1 (rs2229109)) were analyzed using next-generation sequencing. Results: Significant differences in genotype frequencies were observed for SLC19A1 rs1051266 (p = 0.03) and COL18A1 rs9977268 (p = 0.02). Carriers of the T allele in both genes were more frequent among patients requiring biologic therapy, suggesting a possible association with MTX intolerance or reduced efficacy. Conclusions: The study revealed an association between polymorphisms in the SLC19A1 rs1051266 and COL18A1 rs9977268 genes and the need to switch from MTX to biologic therapy in patients with moderate-to-severe psoriasis. These findings suggest that carriers of the C allele in these genes may have an increased risk of methotrexate intolerance. Full article

Background/Objectives: Dolutegravir (DTG) is recommended as first-line treatment for Thai people living with HIV (PLWH). Real-world studies show high plasma concentration variability, which may increase neuropsychiatric adverse effects. This variability can be influenced by both genetic and nongenetic factors, but data for the Thai population are insufficient. We investigated factors associated with DTG pharmacokinetics in Thai PLWH. Methods: A cross-sectional analysis was conducted in Thai PLWH receiving a 50 mg DTG-based regimen. Intensive blood sampling was performed to determine DTG pharmacokinetic parameters using a non-compartmental analysis. Genotyping for UGT1A1, ABCG2, and NR1I2 was performed. Univariable and multivariable linear regression analyses were used to identify factors associated with DTG pharmacokinetics. Results: A total of 104 Thai PLWH were included. Multivariable analysis demonstrated that both the UGT1A1 poor metabolizer phenotype and body weight were independently associated with DTG exposure. After adjusting for body weight, the UGT1A1 poor metabolizer phenotype was associated with increases of 5.18% in AUC_0–24 and 20.59% in C_trough. No significant association was found between the ABCG2 421 C>A polymorphism and DTG pharmacokinetic parameters. Conclusions: Body weight and the UGT1A1 poor metabolizer phenotype significantly impacted DTG exposure in Thai PLWH. Those with the UGT1A1 poor metabolizer, particularly with lower body weight, had significantly increased DTG exposures. These findings highlight that dose optimization may be worth exploring in selected individuals in this population. Full article

Objectives: This study aimed to elucidate the determinants of interindividual variability in the pharmacokinetics of ibrutinib among healthy Chinese subjects, focusing on the influence of demographic characteristics, dietary conditions, and genetic polymorphisms on CYP enzymes and ABC transporters. Methods: Thirty-two participants were randomly assigned to either a fasting (n = 16) or fed (n = 16) group, each receiving a single 140 mg oral dose of ibrutinib. Plasma concentrations were quantified using a validated UPLC–MS/MS method. Genetic polymorphisms in CYP3A4, CYP3A5, CYP2D6, and ABCG2 were identified by Sanger sequencing. Pharmacokinetic parameters, including apparent clearance (CL/F), maximum plasma concentration (Cmax), area under the plasma concentration–time curve (AUC0-t), and time to maximum concentration (Tmax), were estimated by non-compartmental analysis and statistically evaluated for associations with demographic, dietary, and genetic variables. Results: Food intake significantly affected ibrutinib pharmacokinetics, with postprandial administration resulting in reduced CL/F and increased Cmax and AUC0-t (p < 0.01). Gender differences were also observed, as females exhibited higher CL/F, lower Cmax, and AUC0-t than males (p < 0.05). The CYP2D6 c.100C>T polymorphism significantly decreased CL/F and increased exposure in fasting and male subjects (p < 0.05), but this effect was absent under fed conditions. Conversely, the ABCG2 c.421C>A variant was associated with increased CL/F and decreased AUC0-t (p < 0.05), while other genotypes exerted negligible effects. Conclusions: Ibrutinib pharmacokinetics are significantly modulated by dietary status, gender, and genetic polymorphisms, particularly CYP2D6 c.100C>T and ABCG2 c.421C>A. These findings underscore the importance of integrating pharmacogenetic and physiological factors into individualized dosing strategies to optimize therapeutic efficacy and minimize adverse effects. Full article

Background/Objectives: Methotrexate (MTX) is currently the most widely used treatment for Rheumatoid Arthritis (RA) due to its demonstrated efficacy and well-known safety profile. However, the effectiveness and toxicity of MTX can vary among patients, partly due to genetic factors. Therefore, this study aimed to investigate the associations between the polymorphisms in the ABC subfamily G member 2 (ABCG2) gene and MTX effectiveness/toxicity in Saudi Arabia RA patients. Methods: The study is a retrospective, multicenter, case–control study that uses Sanger sequencing techniques for genotyping. Results: More than half of the patients (55.56%) were poor responders, with a slightly higher mean age. However, there was no significant difference between the two groups, not only in terms of age but also in other demographics and clinical factors. Regarding the rs2231137 polymorphism, the CC, CT, and TT genotype frequency were 91%, 7%, and 2%, respectively. The mutated variant (TT) was only observed in the positive rheumatoid factor group. Notably, none of these genotypes displayed any significant correlation with demographic characteristics, clinical features, or MTX efficacy/toxicity. Conclusions: This study is the first pharmacogenetic study of rs2231137 polymorphism in RA patients utilizing linear regression, revealing that rs2231137 polymorphism is not a predictor of either MTX efficacy or toxicity in RA patients. Therefore, more research is needed. Full article

Background/Objectives: Ibrutinib is a selective Bruton’s tyrosine kinase inhibitor approved for the treatment of chronic lymphocytic leukemia (CLL). This drug exhibits significant variability in response and toxicity profile, possibly due to genetic polymorphisms in drug-metabolizing enzymes and transporters. The aim of this observational study is to address interindividual variability in the efficacy and safety of ibrutinib treatment in 49 CLL patients. Methods: Genotyping of nine polymorphisms was performed by quantitative polymerase chain reaction (qPCR) using a ViiA7^® PCR Instrument and TaqMan assays, and ibrutinib plasma concentrations were determined using high-performance liquid chromatography coupled to a tandem mass spectrometry detector (HPLC-MS/MS). Results: Our study confirmed a high response rate, with 62% of patients achieving complete remission (CR), 9% CR with incomplete hematologic recovery (CRi), and 24% partial remission (PR). The impact of genetic polymorphisms on the CR rate was evaluated, revealing no statistically significant associations for CYP3A4, CYP3A5, ABCB1, ABCG2, and SLCO1B1 variants. However, a tendency was observed for patients carrying ABCB1 rs1128503, rs1045642 T/T, or rs2032582 A/A genotypes to achieve a higher CR rate. Adverse drug reactions (ADRs) were frequent, with vascular disorders (39%) and infections (27%) being the most common. Genetic polymorphisms influenced ibrutinib toxicity, with CYP3A4 *1/*22 appearing to be protective against overall ADRs. Conclusions: The unexpected association between CYP3A4 *1/*22 genotype and lower ADR incidence, as well as the trend toward improved treatment response in patients carrying ABCB1 genotypes, suggests compensatory metabolic mechanisms. However, given the small sample size, larger studies are needed to confirm these findings and their clinical implications, while also aiming to uncover other non-genetic factors that may contribute to a better understanding of the variability in treatment response and toxicity. Full article

Objectives: The study investigates runs of homozygosity (ROH) and heterozygosity (ROHet), and their patterns in nine sheep breeds (772 animals in total) maintained in Poland (native and conserved), corresponding to their genetic diversity, inbreeding levels, and selection signatures. Methods: Genotypes were obtained using the Illumina OvineSNP50 BeadChip and quality-filtered SNPs were used to detect ROH and ROHet segments with the detectRUNS R package, following stringent parameters for segment length, SNP density, and genotype quality. Results: Significant variation in ROH characteristics was observed across breeds. Short ROH segments were predominant in all breeds, indicating historical inbreeding events. In contrast, longer ROH segments signified recent inbreeding, particularly in Swiniarka (SW) and Polish Merino of Colored Variety (MPC). The ROH-based genomic inbreeding coefficient (F_ROH) varied across breeds, with SW exhibiting the highest levels, suggesting reduced genetic diversity. ROHet analysis revealed that Uhruska (UHR) had the highest heterozygous segments span, while Black-headed (BH) sheep exhibited the lowest ROHet extent. ROH islands identified across breeds revealed regions under selection, associated with traits such as reproductive performance, wool quality, and body condition. Genes located within these islands (e.g., U6, SPP1, ABCG2) were linked to economically significant traits including milk production, growth, and carcass quality. Conclusions: The presented results highlight the genetic adaptations shaped by selection pressures, while also providing insights into the genetic architecture of sheep breeds maintained in Poland. Full article

Background: Sitosterolemia is a rare autosomal recessive disorder characterized by diverse clinical manifestations ranging from asymptomatic cases to the development of xanthomas, hypercholesterolemia, premature atherosclerosis, or even sudden death during childhood. It results from homozygous or compound heterozygous pathogenic variants in the ABCG5 or ABCG8 genes. Prompt detection and intervention are essential to managing this condition and preventing severe outcomes. Methods: This study aims to retrospectively analyze the phenotype, genotype, treatment, and outcomes of 14 children—seven boys and seven girls—all of Vietnamese origin, diagnosed with sitosterolemia at the Vietnam National Children’s Hospital between March 2015 and July 2024. Results: The median ages at disease onset and diagnosis were 5.7 years (range: 1.5–17.9) and 7.2 years (range: 1.7–17.9), respectively. Xanthomas were observed in 85.7% of patients (12/14), arthralgia in 14.3% (2/14), and anemia in 7.1% (1/14), with no cases of thrombocytopenia. At diagnosis, all patients exhibited elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), with considerably higher levels in patients with xanthomas compared to those without. Mutations in the ABCG5 gene were identified in 71.4% (10/14) of the patients, while 28.6% (4/14) had mutations in the ABCG8 gene. Fourteen variants were detected, nine in ABCG5 and five in ABCG8, with five variants reported for the first time in sitosterolemia patients. Initial management for all patients involved dietary modifications. After three months, 10 patients with persistently elevated TC and LDL-C received ezetimibe or cholestyramine treatment. Among the eight patients who continued treatment for over three months, the median TC and LDL-C concentrations decreased by 54.9% and 67.3%, respectively. Conclusions: Among Vietnamese patients with sitosterolemia, variants in the ABCG5 gene were more prevalent than those in the ABCG8 gene. Patients showed a positive response to ezetimibe or cholestyramine treatment. Genetic testing is essential for establishing a diagnosis of sitosterolemia and guiding accurate management strategies. Full article

Statins are the primary drugs used to prevent cardiovascular disease by inhibiting the HMG-CoA reductase, an enzyme crucial for the synthesis of LDL cholesterol in the liver. A significant number of patients experience adverse drug reactions (ADRs), particularly musculoskeletal problems, which can affect adherence to treatment. Recent clinical guidelines, such as those from the Clinical Pharmacogenetics Implementation Consortium (CPIC) in 2022, recommend adjusting rosuvastatin doses based on genetic variations in the ABCG2 and SLCO1B1 genes to minimize ADRs and improve treatment efficacy. Despite these adjustments, some patients still experience ADRs. So, we performed a candidate gene study to better understand the pharmacogenetics of rosuvastatin. This study included 119 healthy volunteers who participated in three bioequivalence trials of rosuvastatin alone or in combination with ezetimibe at the Clinical Trials Unit of the Hospital Universitario de La Princesa (UECHUP). Participants were genotyped using a custom OpenArray from ThermoFisher that assessed 124 variants in 38 genes associated with drug metabolism and transport. No significant differences were observed according to sex or biogeographic origin. A significant increase in t_1/2 (p_multivariate(p_mv) = 0.013) was observed in the rosuvastatin plus ezetimibe trial compared with the rosuvastatin alone trials. Genetic analysis showed that decreased (DF) and poor function (PF) volunteers for the ABCG2 transporter had higher AUC_∞/DW (adjusted dose/weight), AUC_72h/DW and C_max/DW compared to normal function (NF) volunteers (p_mv< 0.001). DF and PF volunteers for SLCO1B1 showed an increase in AUC_72h/DW (p_mv = 0.020) compared to increased (IF) and NF individuals. Results for ABCG2 and SLCO1B1 were consistent with the existing literature. In addition, AUC_∞/DW, AUC_72h/DW and C_max/DW were increased in intermediate (IA) and poor (PA) NAT2 acetylators (p_mv = 0.001, p_mv< 0.001, p_mv< 0.001, respectively) compared to rapid acetylators (RA), which could be associated through a secondary pathway that was previously unknown. Full article

This systematic review and meta-analysis aimed to verify the association between the genetic variants of adenosine triphosphate (ATP)-binding cassette subfamily B member 1 (ABCB1) and ATP-binding cassette subfamily G member 2 (ABCG2) genes and the presence and severity of gefitinib-associated adverse reactions. We systematically searched PubMed, Virtual Health Library/Bireme, Scopus, Embase, and Web of Science databases for relevant studies published up to February 2024. In total, five studies were included in the review. Additionally, eight genetic variants related to ABCB1 (rs1045642, rs1128503, rs2032582, and rs1025836) and ABCG2 (rs2231142, rs2231137, rs2622604, and 15622C>T) genes were analyzed. Meta-analysis showed a significant association between the ABCB1 gene rs1045642 TT genotype and presence of diarrhea (OR = 5.41, 95% CI: 1.38–21.14, I² = 0%), the ABCB1 gene rs1128503 TT genotype and CT + TT group and the presence of skin rash (OR = 4.37, 95% CI: 1.51–12.61, I² = 0% and OR = 6.99, 95%CI: 1.61–30.30, I²= 0%, respectively), and the ABCG2 gene rs2231142 CC genotype and presence of diarrhea (OR = 3.87, 95% CI: 1.53–9.84, I² = 39%). No ABCB1 or ABCG2 genes were positively associated with the severity of adverse reactions associated with gefitinib. In conclusion, this study showed that ABCB1 and ABCG2 variants are likely to exhibit clinical implications in predicting the presence of adverse reactions to gefitinib. Full article

Multidrug resistance (MDR) commonly leads to cancer treatment failure because cancer cells often expel chemotherapeutic drugs using ATP-binding cassette (ABC) transporters, which reduce drug levels within the cells. This study investigated the clinical characteristics and single nucleotide variant (SNV) in ABCB1, ABCC1, ABCC2, ABCC4, and ABCG2, and their association with mortality in pediatric patients with central nervous system tumors (CNST). Using TaqMan probes, a real-time polymerase chain reaction genotyped 15 SNPs in 111 samples. Patients were followed up until death or the last follow-up day using the Cox proportional hazards model. An association was found between the rs1045642 (ABCB1) in the recessive model (HR = 2.433, 95% CI 1.098–5.392, p = 0.029), and the ICE scheme in the codominant model (HR = 9.810, 95% CI 2.74–35.06, p ≤ 0.001), dominant model (HR = 6.807, 95% CI 2.87–16.103, p ≤ 0.001), and recessive model (HR = 6.903, 95% CI 2.915–16.544, p = 0.038) significantly increased mortality in this cohort of patients. An association was also observed between the variant rs3114020 (ABCG2) and mortality in the codominant model (HR = 5.35, 95% CI 1.83–15.39, p = 0.002) and the dominant model (HR = 4.421, 95% CI 1.747–11.185, p = 0.002). A significant association between the ICE treatment schedule and increased mortality risk in the codominant model (HR = 6.351, 95% CI 1.831–22.02, p = 0.004, HR = 9.571, 95% CI 2.856–32.07, p ≤ 0.001), dominant model (HR = 6.592, 95% CI 2.669–16.280, p ≤ 0.001), and recessive model (HR = 5.798, 95% CI 2.411–13.940, p ≤ 0.001). The genetic variants rs3114020 in the ABCG2 gene and rs1045642 in the ABCB1 gene and the ICE chemotherapy schedule were associated with an increased mortality risk in this cohort of pediatric patients with CNST. Full article

Background: Methotrexate (MTX) is one of the most extensively used drugs in the treatment of moderate-to-severe psoriasis (PS). However, it frequently must be suspended owing to the toxicity in certain patients. Objective: To evaluate the influence of ABCC1, ABCG2, and FOXP3 in the development of MTX toxicity in PS. Methods: Retrospective cohort study with 101 patients. Five single-nucleotide polymorphisms (SNPs) were genotyped using real-time polymerase chain reaction with TaqMan probes. Results: Patients carrying ABCC1 rs2238476-AG genotype (AG vs. GG: OR = 8.04; 95% CI = 1.48–46.78; p = 0.015); FOXP3 rs376154-GT and GG genotypes (GT vs. TT/GG: OR = 3.86; 95% CI = 1.17–13.92; p = 0.031) and ABCG2 rs13120400-T allele (T vs. CC: OR = 8.33; 95% CI = 1.24–164.79; p = 0.059) showed a higher risk of developing more than one adverse effect. The toxicity analysis by subtypes showed that the ABCC1 rs2238476-AG genotype (AG vs. GG: OR = 8.10; 95% CI = 1.69–46.63; p = 0.011) and FOXP3 rs376154-GT genotype (OR = 4.11; 95% CI = 1.22–15.30; p = 0.027) were associated with the appearance of asthenia. No association of the other ABCC1 polymorphisms (rs35592 and rs246240) with MTX toxicity was found. Conclusion: ABCC1, ABCG2, and FOXP3 polymorphisms can be considered to be risk biomarkers of toxicities in PS patients treated with MTX. Full article

ABCG5 and ABCG8 are two key adenosine triphosphate-binding cassette (ABC) proteins that regulate whole-body sterol trafficking. This study aimed to elucidate the association between ABCG5/G8 gene region variants and lipid profile, cardiometabolic traits, and gallstone disease history in Taiwan. A total of 1494 Taiwan Biobank participants with whole-genome sequencing data and 117,679 participants with Axiom Genome-Wide CHB Array data were enrolled for analysis. Using genotype–phenotype and stepwise linear regression analyses, we found independent associations of four Asian-specific ABCG5 variants, rs119480069, rs199984328, rs560839317, and rs748096191, with total, low-density lipoprotein (LDL), and non-high-density lipoprotein (HDL) cholesterol levels (all p ≤ 0.0002). Four other variants, which were in nearly complete linkage disequilibrium, exhibited genome-wide significant associations with gallstone disease history, and the ABCG8 rs11887534 variant showed a trend of superiority for gallstone disease history in a nested logistic regression model (p = 0.074). Through regional association analysis of various other cardiometabolic traits, two variants of the PLEKHH2, approximately 50 kb from the ABCG5/G8 region, exhibited significant associations with blood pressure status (p < 10⁻⁶). In conclusion, differential effects of ABCG5/G8 region variants were noted for lipid profile, blood pressure status, and gallstone disease history in Taiwan. These results indicate the crucial role of individualized assessment of ABCG5/G8 variants for different cardiometabolic phenotypes. Full article

Multi-kinase inhibitors (MKIs) represent the best therapeutic option in advanced thyroid cancer patients. The therapeutic efficacy and toxicity of MKIs are very heterogeneous and are difficult to predict before starting treatment. Moreover, due to the development of severe adverse events, it is necessary to interrupt the therapy some patients. Using a pharmacogenetic approach, we evaluated polymorphisms in genes coding for proteins involved with the absorption and elimination of the drug in 18 advanced thyroid cancer patients treated with lenvatinib, and correlated the genetic background with (1) diarrhea, nausea, vomiting and epigastric pain; (2) oral mucositis and xerostomia; (3) hypertension and proteinuria; (4) asthenia; (5) anorexia and weight loss; (6) hand foot syndrome. Analyzed variants belong to cytochrome P450 (CYP3A4 rs2242480 and rs2687116 and CYP3A5 rs776746) genes and to ATP-binding cassette transporters (ABCB1 rs1045642, rs2032582 and rs2235048 and ABCG2 rs2231142). Our results suggest that the GG genotype for rs2242480 in CYP3A4 and CC genotype in rs776746 for CYP3A5 were both associated with the presence of hypertension. Being heterozygous for SNPs in the ABCB1 gene (rs1045642 and 2235048) implicated a higher grade of weight loss. The ABCG2 rs2231142 statistically correlated with a higher extent of mucositis and xerostomia (CC genotype). Heterozygous and rare homozygous genotypes for rs2242480 in CYP3A4 and for rs776746 for CYP3A5 were found to be statistically linked to a worse outcome. Evaluating the genetic profile before starting lenvatinib treatment may help to predict the occurrence and grade of some side effects, and may contribute to improving patient management. Full article