HLA-B*13:01 allele has been identified as the genetic determinant of dapsone hypersensitivity syndrome (DHS) among leprosy and non-leprosy patients in several studies. Dapsone hydroxylamine (DDS-NHOH), an active metabolite of dapsone, has been believed to be responsible for DHS. However, studies have not highlighted the importance of other genetic polymorphisms in dapsone-induced severe cutaneous adverse reactions (SCAR). We investigated the association of HLA alleles and cytochrome P450 (CYP) alleles with dapsone-induced SCAR in Thai non-leprosy patients. A prospective cohort study, 16 Thai patients of dapsone-induced SCARs (5 SJS-TEN and 11 DRESS) and 9 Taiwanese patients of dapsone-induced SCARs (2 SJS-TEN and 7 DRESS), 40 dapsone-tolerant controls, and 470 general Thai population were enrolled. HLA class I and II alleles were genotyped using polymerase chain reaction-sequence specific oligonucleotides (PCR-SSOs). CYP2C9, CYP2C19, and CYP3A4 genotypes were determined by the TaqMan real-time PCR assay. We performed computational analyses of dapsone and DDS-NHOH interacting with HLA-B*13:01 and HLA-B*13:02 alleles by the molecular docking approach. Among all the HLA alleles, only HLA-B*13:01 allele was found to be significantly associated with dapsone-induced SCARs (OR = 39.00, 95% CI = 7.67–198.21, p = 5.3447 × 10−7), SJS-TEN (OR = 36.00, 95% CI = 3.19–405.89, p = 2.1657 × 10−3), and DRESS (OR = 40.50, 95% CI = 6.38–257.03, p = 1.0784 × 10−5) as compared to dapsone-tolerant controls. Also, HLA-B*13:01 allele was strongly associated with dapsone-induced SCARs in Asians (OR = 36.00, 95% CI = 8.67–149.52, p = 2.8068 × 10−7) and Taiwanese (OR = 31.50, 95% CI = 4.80–206.56, p = 2.5519 × 10−3). Furthermore, dapsone and DDS-NHOH fit within the extra-deep sub pocket of the antigen-binding site of the HLA-B*13:01 allele and change the antigen-recognition site. However, there was no significant association between genetic polymorphism of cytochrome P450 (CYP2C9, CYP2C19, and CYP3A4) and dapsone-induced SCARs (SJS-TEN and DRESS). The results of this study support the specific genotyping of the HLA-B*13:01 allele to avoid dapsone-induced SCARs including SJS-TEN and DRESS before initiating dapsone therapy in the Asian population.
Aims Carbamazepine (CBZ) is one of the most common causative drugs of severe cutaneous adverse drug reactions (SCARs) including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reactions with eosinophilia and systemic symptoms. Although genetic polymorphisms of the human leucocyte antigens (HLA) are well recognized key elements for the susceptibility to CBZ‐induced SCARs, some evidence suggest that polymorphisms of microsomal epoxide hydrolase 1 (EPHX1) may also contribute to the risk of these SCARs. This study investigated the association between the HLA and EPHX1 polymorphisms on CBZ‐induced SCARs in large sample sizes and well‐defined SCARs patients. Methods Ninety‐one CBZ‐induced SCARs Thai patients and 144 CBZ‐tolerant patients were enrolled in the study. The genotypes of HLA‐A, HLA‐B and EPHX1 were determined. Results Only 2 HLA alleles including HLA‐B*15:02 and HLA‐A*24:07 were statistically significant association with CBZ‐induced SJS/TEN. The highest risk was observed in patients with HLA‐B*15:02 allele (OR = 44.33, 95% confidence interval = 20.24–97.09, corrected P‐value = 6.80 × 10−29). Moreover, HLA‐B75 serotypes were significantly associated with CBZ‐induced SJS/TEN groups with an odds ratio of 81.00 (95% confidence interval = 32.39–202.56, corrected P‐value = 3.84 × 10−34). There is no association between EPHX1 c.337 T > C polymorphism and all phenotypes of CBZ‐induced SCARs. Conclusion The HLA‐B*15:02 allele is the strongest genetic marker for the prediction of SJS/TEN induced by CBZ in Thai population. Screening for other alleles in the HLA‐B75 serotype increases sensitivity for prediction of a life‐threatening SCARs caused by CBZ.
Objective: To study the clinical features and associated factors of female pattern hair loss (FPHL) in premenopausal and menopausal women patients. Materials and Methods: This is a retrospective chart review of FPHL patients visited hair clinic, Siriraj Hospital from June 2012 to May 2015. Demographic data, family history and history of hair loss were evaluated. Factors associated with FPHL were analysed. Results: There were 267 patients (180 premenopausal women and 87 menopausal women) in this study. The mean age of onset of patients was 35.5±12 years (premenopausal FPHL) and 60.5±7 years (menopausal FPHL). Positive family history of androgenetic alopecia (AGA) was 48.3%, mainly in first-degree relatives. The data showed an increased incidence of FPHL with advancing age. The most common presentation is Ludwig grade I. The study showed that patients also have dyslipidemia (16.9%), hypertension (16.5%), diabetes mellitus (10.9%), hypothyroidism (4.9%), anemia (3.7%), and hyperthyroidism (2.9%). In multivariate analysis, significant associations were found between low ferritin level < 70 µg/L and premenopausal FPHL (OR 5.51, 95% CI 2.26-15.14, P = 0.01). Conclusion: Maternal family history of AGA seems to have a greater influence on premenopausal FPHL. Low serum ferritin levels < 70 µg/L were significantly associated with FPHL in premenopausal women.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.