Kim HJ, et al. Korean J Physiol Pharmacol. 2009 Aug;13(4):281-285. http://dx.doi.org/10.4196/kjpp.2009.13.4.281

Estrogen and estrogen receptors (ERs) are known to play important roles in the pathophysiology of osteoarthritis (OA). To investigate ER-alpha gene polymorphisms for its associations with primary knee OA, we conducted a case-control association study in patients with primary knee OA (n = 151) and healthy individuals (n = 397) in the Korean population. Haplotyping analysis was used to determine the relationship between three polymorphisms in the ER-alpha gene (intron 1 T/C, intron 1 A/G and exon 8 G/A) and primary knee OA. Genotypes of the ER-alpha gene polymorphism were determined by PCR followed by restriction enzyme digestion (PvuII for intron 1 T/C, XbaI for intron 1 A/G, and BtgI for exon 8 G/A polymorphism). There was no significant difference between primary knee OA patients and healthy control individuals in the distribution of any of the genotypes evaluated. However, we found that the allele frequency for the exon 8 G/A BtgI polymorphism (codon 594) was significantly different between primary knee OA patients and control individuals (odds ratio = 1.38, 95% confidence interval = 1.01-1.88; P = 0.044). In haplotype frequency estimation analysis, there was a significant difference between primary knee OA patients and control individuals (degrees of freedom = 7, chi2 = 21.48; P = 0.003). Although the number OA patients studied is small, the present study shows that ER-alpha gene haplotype may be associated with primary knee OA, and genetic variations in the ER-alpha gene may be involved in OA.

Background: The occurrence of aberrant functional connectivity in the neuronal circuit is one of the integrative theories of the etiology of schizophrenia. Previous studies have reported that the protein and mRNA levels of the synapsin 2 (SYN2) and complexin 2 (CPLX2) genes were decreased in patients with schizophrenia. Synapsin 2 and complexin 2 are involved in synaptogenesis and the modulation of neurotransmitter release. This report presents a study of the association of polymorphisms ofSYN2andCPLX2with schizophrenia in the Korean population.Methods: Six single nucleotide polymorphisms (SNPs) and one 5-bp insertion/deletion inSYN2and five SNPs inCPLX2were genotyped in 154 Korean patients with schizophrenia and 133 control patients using direct sequencing or restriction fragment length polymorphism analysis. An intermarker linkage disequilibrium map was constructed for each gene.Results: Although there was no significant difference in the genotypic distributions and allelic frequencies of eitherSYN2orCPLX2polymorphisms between the schizophrenia and control groups, the two-way haplotype analyses revealed significant associations with the disease (P< 0.05 after Bonferroni correction). The three-way haplotype analyses also revealed a significant association ofSYN2with schizophrenia (P< 0.001 after Bonferroni correction).Conclusion: These results suggest that bothSYN2andCPLX2may confer susceptibility to schizophrenia in the Korean population.

Summary: The protective effect of topiramate (TPM) on seizure‐induced neuronal injury is well known; however, its molecular basis has yet to be elucidated. We investigated the effect and signaling mediators of TPM on seizure‐induced hippocampal cell death in kainic acid (KA)‐treated ICR mice. KA‐induced hippocampal cell death was identified by terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling. Immunoreactivity (IR) of p‐Erk, p‐Jnk, p‐P38, and caspase‐3, and caspase‐3 activity were observed in the hippocampal region 3 h after KA (0.1 μg/5 μL, i.c.v.) administration, and/or TPM (100 mg/kg, i.p.) pretreatment. TPM attenuated seizure‐induced neuronal cell death and reduced KA‐induced p‐Erk IR in the CA3 region of the hippocampus, but did not affect p‐Jnk and p‐P38. In addition, TPM reduced caspase‐3 IR and activation by KA. KA‐induced seizures were also suppressed by TPM pretreatment. TPM inhibits seizures, and decreases Erk phosphorylation and caspase‐3 activation by KA, thereby contributing to protection from neuronal injury.