Spectrum of cutaneous adverse reactions to aromatic antiepileptic drugs and human leukocyte antigen genotypes in Thai patients and meta-analysis

Aromatic antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs) add up to the limited use of the AEDs in the treatment and prevention of seizures. Human leukocyte antigen-B (HLA-B) alleles have been linked to AEDs-induced cADRs. We investigated the association between cADRs (including Stevens–Johnson syndrome; SJS/toxic epidermal necrolysis; TEN, drug reaction with eosinophilia and systemic symptoms; DRESS, and Maculopapular eruption; MPE) caused by AEDs (phenytoin, carbamazepine, lamotrigine, phenobarbital and oxcarbazepine) and HLA-B alleles in Thai population. Through the case-control study, 166 patients with AEDs-induced cADRs, 426 AEDs-tolerant patients (AEDs-tolerant controls), and 470 healthy subjects (Thai population) were collected. The HLA genotypes were detected using the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. We also performed a meta-analysis with these data and other populations. The carrier rate of HLA-B*15:02 was significantly different between AEDs-induced cADRs group and AEDs-tolerant group (Odds ratio; OR 4.28, 95% Confidence interval; CI 2.64–6.95, p < 0.001), AEDs-induced cADRs group and Thai population (OR 2.15, 95%CI 1.41–3.29, p < 0.001). In meta-analysis showed the strong association HLA-B*15:02 with AEDs-induced cADRs (OR 4.77, 95%CI 1.79–12.73, p < 0.001). Furthermore, HLA-B*15:02 was associated with SJS/TEN induced by AEDs (OR 10.28, 95%CI 6.50–16.28, p < 0.001) Phenytoin (OR 4.12, 95%CI 1.77–9.59, p = 0.001) and carbamazepine (OR 137.69, 95%CI 50.97–371.98, p < 0.001). This study demonstrated that genetic association for AEDs-induced cADRs was phenotype-specific. A strong association between HLA-B*15:02 and AEDs-induced SJS/TEN was demonstrated with an OR of 10.79 (95%CI 5.50–21.16, p < 0.001) when compared with AEDs-tolerant group. On the other hand, the carrier rates of HLA-B*08:01, HLA-B*13:01, and HLA-B*56:02 were significantly higher in the DRESS group compared with the AEDs-tolerant group (p = 0.029, 0.007, and 0.017, respectively). The HLA-B*15:02 allele may represent a risk factor for AEDs-induced cADRs.

HLA-B60 and HLA-DR4 alleles in Javanese children with steroid-sensitive primary nephrotic syndrome

Background Steroid-sensitive nephrotic syndrome (SSNS) ofchildren is associated with several human leucocyte antigen (HLA)class I and class II.Objective To investigate the association between HLA-B60 andHLA-DR4 alleles and primary nephrotic syndrome (PNS) inJavanese children.Methods A case control study was conducted on 47 Javanesechildren with PNS who were typed for HLA-B60 and HLA-DR4 al-leles, using DNA sequence specific oligonucleotide probe (SSOP)as control sample, 47 healthy children were also typed for thoseHLA antigens using the same technique.Results Compared with control group, children with PNS had higherfrequency of both HLA-B60 (23.32% vs 4.3%; OR=6.85 [CI=1.32-35.65]; P<0.01) and HLA-DR4 (40.0% vs 2.1%; OR=30.67 [CI:3.71-253.33]; P<0.0002). There was association between HLA and PNSwith SSNS in children.Conclusion The strong association between PNS and HLA anti-gen support the immunogenetic background of the disease, whichseems to be stronger in young children with SSNS.

Significant Association ofHLA-BAlleles and Genotypes in Thai Children with Autism Spectrum Disorders: A Case-Control Study

Autism is a severe neurodevelopmental disorder. Many susceptible causative genes have been identified. Most of the previous reports showed the relationship between the Human Leukocyte Antigen (HLA) gene and etiology of autism. In order to identifyHLA-Balleles associated with autism in Thai population, we compared the frequency ofHLA-Ballele in 364 autistic subjects with 952 normal subjects by using a two-stage sequence-specific oligonucleotide probe system (PCR-SSOP) method based on flow-cytometry technology.HLA-B⁎13:02(P=0.019, OR = 2.229),HLA-B⁎38:02(P=0.049, OR = 1.628),HLA-B⁎44:03(P=0.016, OR = 1.645), andHLA-B⁎56:01(P= 1.78 × 10−4, OR = 4.927) alleles were significantly increased in autistic subjects compared with normal subjects. Moreover, we found that theHLA-B⁎18:02(P=0.016, OR = 0.375) andHLA-B⁎46:12(P=0.008, OR = 0.147) alleles were negatively associated with autism when compared to normal controls. Both alleles might have a protective role in disease development. In addition, fourHLA-Bgenotypes of autistic patients had statistically significant relationship with control groups, consisting ofHLA-B⁎3905/⁎5801(P=0.032, OR = 24.697),HLA-B⁎2704/⁎5801(P=0.022, OR = 6.872),HLA-B⁎3501/⁎4403(P=0.021, OR = 30.269), andHLA-B⁎1801/⁎4402(P = 0.017, OR = 13.757). This is the first report onHLA-Bassociated with Thai autism and may serve as a marker for genetic susceptibility to autism in Thai population.