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Genin E.,University Paris Diderot | Chen D.-P.,Chang Gung University | Hung S.-I.,National Yang Ming University | Sekula P.,Albert Ludwigs University of Freiburg | And 18 more authors.
Pharmacogenomics Journal | Year: 2014

HLA-A*31:01 was reported to be associated with carbamazepine (CBZ)-induced severe cutaneous adverse reactions (SCAR), including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We conducted an international study using consensus diagnosis criteria to enroll a total of 93 patients with CBZ-SCAR from Europe or Asia. We found that HLA-A*31:01 showed a significant association with CBZ-DRESS in Europeans (P<0.001; odds ratio (OR) (95% confidence interval (CI))=57.6 (11.0-340)), and the strong association was also found in Chinese (P<0.001; OR (95% CI)=23.0 (4.2-125)). However, HLA-A*31:01 had no association with CBZ-SJS/TEN in neither Chinese nor Europeans. By comparison, HLA-B*15:02 showed a strong association with CBZ-SJS/TEN in Chinese (P<0.001, OR (95% CI)=58.1 (17.6-192)). A meta-analysis of this and other published studies confirmed that in all populations, HLA-A*31:01 had an extremely strong association with CBZ-DRESS (P<0.001, a pooled OR (95% CI)=13.2 (8.4-20.8)), but a much weaker association with CBZ-SJS/TEN (P=0.01, OR (95% CI)=3.94 (1.4-11.5)). Our data revealed that HLA-A*31:01 is a specific predictor for CBZ-DRESS but not for CBZ-SJS/TEN. More studies are needed to investigate the genetic determinant of CBZ-SJS/TEN in Europeans. Considering the potential clinical utility, the cost-effectiveness of the combined HLA-A*31:01 and HLA-B*15:02 genetic test to prevent CBZ-SCAR in Chinese needs further investigation. © 2014 Macmillan Publishers Limited. Source


Hizem S.,University of Monastir | Mtiraoui N.,University of Monastir | Mtiraoui N.,University of Tabuk | Massaoudi S.,University of Monastir | And 9 more authors.
American Journal of Reproductive Immunology | Year: 2014

Problem: To investigate the possible association of Natural Killer Group (NKG) receptors gene polymorphisms and MHC class I chain-related protein A (MICA) gene polymorphism with recurrent miscarriage (RM). Methods: Seven SNPs in NKG2D gene (rs1049174, rs2255336, rs2617160, rs2617161, rs2246809, rs2617169, and rs2617170), one SNP in NKG2A gene (rs1983526), and one SNP in MICA gene (MICA129) were assessed by allelic discrimination (real-time PCR) in both patients and control women. Results: The rs2617170 T/T genotype significantly protected against RM [OR (95%) = 0.63 (0.40-0.98)]. The NKG2D haplotypes analysis on the basis of pairwise LD revealed two haplotype blocks. In block1, we found an increased frequency of CAT (Pc = 0.007; OR = 2.13; 95% CI = 1.24-3.68) and GGA haplotypes (Pc = 0.041; OR = 2.02; 95%CI = 1.03-3.96) and reduced frequency of CAA haplotype (Pc = 0.027; OR = 0.72; 95% CI = 0.54-0.96) in patients. In block2, increased frequency of GATG haplotype (Pc = 10-4; OR = 9.25; 95% CI = 3.04-28.12) and reduced frequency of ATTC haplotype (Pc = 0.035; OR = 0.69; 95%CI = 0.50-0.97) were seen in patients. Conclusion: The NKG2D gene polymorphisms may influence the success of pregnancy in Tunisian women. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Source

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