Roles of osteocyte apoptosis in steroid-induced avascular necrosis of the femoral head.

An animal model of steroid-induced avascular necrosis of the femoral head (SANFH) was established to investigate the roles of osteocyte apoptosis in this process. Forty five-month-old male and female Japanese white rabbits were randomly divided into groups A (hormone + endotoxin), B (hormone alone), C (endotoxin alone), and D (blank control). Animals were sacrificed two and four weeks following the final treatment (N = 5 for each group at each time point). Bilateral femoral heads were fixed and decalcified, and empty lacunae were counted by hematoxylin staining. At weeks 2 and 4, the empty lacunae percentage was significantly higher in group A than that in groups B, C, or D (P < 0.01), while no significant difference was observed between these latter three. At week 2, all osteocyte apoptosis indexes were within normal ranges in all the groups, which therefore did not significantly differ in this respect (P > 0.05). However, at week 4, the apoptotic index was significantly higher in group A than that in groups B, C, or D (P < 0.01), comparisons between which revealed no such differences. Moreover, a positive correlation was observed between the percentage of empty lacunae and the apoptotic index at week 4 in group A (r = 0.893). We conclude that osteocyte apoptosis plays an important role in SANFH.

NAT2 and CYP2E1 polymorphisms and susceptibility to first-line anti-tuberculosis drug-induced hepatitis.

BACKGROUND: Most cases with anti-tuberculosis drug-induced hepatotoxicity (ATDH) have been attributed to isoniazid. OBJECTIVE: To evaluate whether the polymorphisms of the cytochrome P450 2EI (CYP2E1) and N-acetyltransferase 2 (NAT2) gene are associated with ATDH. DESIGN: A total of 140 tuberculosis (TB) patients without liver diseases before treatment who received anti-tuberculosis treatment were followed prospectively. Their CYP2E1 and NAT2 genotypes were determined using the TaqMan polymerase chain reaction assay. RESULTS: Forty-five (32.1%) patients were diagnosed with ATDH. No significant differences were reported in age and sex between patients with and without ATDH. Slow acetylators defined by NAT2 genotypes had a higher risk of hepatotoxicity than rapid acetylators (51.2% vs. 25.2%, P = 0.0026). Odds ratio (OR) analysis showed that slow acetylator status (OR 3.15, 95%CI 1.47-6.48) was the only independent risk factor for ATDH. Pyrazinamide co-administration induced hepatitis was also associated with NAT2 acetylator status. CYP2E1 c1/c1 homozygotes are prone to developing more severe hepatotoxicity than other c1/c2 and c2/c2 genotypes. CONCLUSION: The slow acetylator status of NAT2 is a significant susceptibility risk factor for ATDH. CYP2E1 is associated with the severity of ATDH.

The polymorphisms of interleukin 17A (IL17A) gene and its association with pediatric asthma in Taiwanese population.

BACKGROUND: The interleukin 17A (IL17A) gene, located on chromosome 6p and linked to asthma phenotype, is a highly potential candidate gene conferring asthma susceptibility. The purpose of this study was to investigate the genetic association between single nucleotide polymorphisms (SNPs) of IL17A and asthma in Taiwanese children. METHODS: We selected and performed genotyping on nine SNPs that encompass the genomic region of IL17A in Taiwanese children with or without asthma. A total of 1939 subjects containing 1027 subjects in testing group and 931 subjects in validation group were recruited in this study. RESULTS: After Bonferroni correction, SNP rs8193036 was found to have a weak association (P = 0.0074 x 9 = 0.066) in genotype frequency test. This association was confirmed by validation group. Logistic regression adjusted allergy comorbidity and gender showed a slightly weaker association. CONCLUSIONS: The results indicated an independent role of IL17A promoter polymorphism rs8193036 in the association with pediatric asthma in Taiwanese population.

The genetic differences with whole genome linkage disequilibrium mapping between responder and non-responder in interferon-alpha and ribavirin combined therapy for chronic hepatitis C patients.

Interferon-alpha and ribavirin combined therapy has been a mainstream treatment for hepatitis C infection. The efficacy of this combined treatment is around 30% to 60%, and the factors affecting the responsiveness are still poorly defined. Our study is intended to investigate the genetic differences between responder and non-responder patients. The genome-wide linkage disequilibrium screening for loci associated with genetic difference between two patient groups was conducted by using 382 autosomal short tandem repeat (STR) markers involving 92 patients. We have identified 19 STR markers displaying different allele frequencies between the two patient groups. In addition, based on their genomic location and biological function, we selected the CD81 and IL15 genes to perform single nucleotide polymorphism genotyping. In conclusion, this study may provide a new approach for identifying the associated polymorphisms and the susceptible loci for interferon-alpha and ribavirin combined therapy in patients with chronic hepatitis C.

Single nucleotide polymorphisms and haplotype of MD-1 gene associated with high serum IgE phenotype with mite-sensitive allergy in Taiwanese children.

MD-1 (myeloid differentiation 1; also known as Ly86, lymphocyte antigen 86), interacting with RP105, plays an important role in Toll-like receptor 4 (TLR4) signalling pathway. It has been suggested to be involved in the pathological mechanism of inflammation and atopic diseases. The purpose of this study was to investigate the genetic association between single nucleotide polymorphisms (SNPs) of MD-1 promoter and coding region and mite-sensitive allergy in Taiwanese children. We conducted a case-control study on 237 controls and 281 allergic patients sensitive to Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f) by genotyping 35 SNPs in MD-1 gene region. In the promoter region we identified three SNPs, rs1334710, rs4959389, and rs977785 that are associated with mite-sensitive allergy in Taiwanese children. The P-values ranged from 0.0150 to 0.009. The haplotypes including promoter region were also associated with mite-sensitive allergy. Our results suggested that MD-1 could be a susceptible gene for mite-sensitive allergy in Taiwanese children.