Objective. Recent genome-wide association scans and replication studies of European populations have disclosed several single-nucleotide polymorphisms (SNPs) associated with rheumatoid arthritis (RA) susceptibility. The aim of this study was to evaluate the RA-associated loci by genotyping previously reported SNPs and additional tag SNPs in a Korean population.Methods. A total of 1,316 unrelated RA patients and 1,006 controls were genotyped for 12 SNPs identified in genome-wide scans and for 12 additional tag SNPs in IL2RB, OLIG3-TNFAIP3, PTPN22, and TRAF1-C5, and the findings were statistically compared.Results. None of the SNPs tested was associated with RA susceptibility, except rs7021206 in TRAF1 intron 3 (P ‫؍‬ 0.0032) and, among the SNPs previously reported, rs6457617 in HLA (P ‫؍‬ 4.6 ؋ 10 ؊35 ). The association of rs7021206 was positive in patients who were seropositive for rheumatoid factor (P ‫؍‬ 0.0051) or for anti-cyclic citrullinated peptide autoantibodies (P ‫؍‬ 0.0062). However, Korean patients were negative for the association of rs3761847 in the TRAF1-C5 intergenic region previously reported in Caucasians. Linkage disequilibrium between rs3761847 and rs7021206 was not as high in Koreans (r 2 ‫؍‬ 0.37) as in Caucasians (r 2 ‫؍‬ 0.67), which explains the lack of association of rs3761847 in Koreans. Accordingly, RA susceptibility was localized to an extended haplotype marked by rs7021206 rather than rs3761847, and SNPs highly correlated with rs7021206 (r 2 > 0.81) extended from rs1953126 in the PHF19-TRAF1 intergenic region to rs2900180 in the TRAF1-C5 intergenic region, spanning 66 kb.Conclusion. Our results demonstrate that within and around TRAF1, excluding PHF19 and C5, SNPs highly correlated with rs7021206, but not those correlated with rs3761847, are associated with RA in both Asians and Caucasians and are possibly correlated with causative variations.

Stuttering is a common neurodevelopmental disorder that has been associated with mutations in genes involved in intracellular trafficking. However, the cellular mechanisms leading to stuttering remain unknown. Engineering a mutation in N-acetylglucosamine-1-phosphate transferase subunits α and β (GNPTAB) found in humans who stutter into the mouse Gnptab gene resulted in deficits in the flow of ultrasonic vocalizations similar to speech deficits of humans who stutter. Here we show that other human stuttering mutations introduced into this mouse gene, Gnptab Ser321Gly and Ala455Ser, produce the same vocalization deficit in 8-day-old pup isolation calls and do not affect other nonvocal behaviors. Immunohistochemistry showed a marked decrease in staining of astrocytes, particularly in the corpus callosum of the Gnptab Ser321Gly homozygote mice compared to wild-type littermates, while the staining of cerebellar Purkinje cells, oligodendrocytes, microglial cells, and dopaminergic neurons was not significantly different. Diffusion tensor imaging also detected deficits in the corpus callosum of the Gnptab Ser321Gly mice. Using a range of cell type-specific Cre-drivers and a Gnptab conditional knockout line, we found that only astrocyte-specific Gnptab-deficient mice displayed a similar vocalization deficit. These data suggest that vocalization defects in mice carrying human stuttering mutations in Gnptab derive from abnormalities in astrocytes, particularly in the corpus callosum, and provide support for hypotheses that focus on deficits in interhemispheric communication in stuttering.

Objective. Anti-cyclic citrullinated peptide (anti-CCP) antibodies are rheumatoid arthritis (RA)-specific serologic markers. RA susceptibility has been associated with HLA-DRB1 shared epitope (SE) alleles and single-nucleotide polymorphism (SNP) haplotypes in the peptidyl arginine deiminase 4 gene (PADI4). This study was undertaken to determine whether anti-CCP levels are associated with PADI4 haplotypes and/or SE alleles in Korean patients with RA.Methods. Three nonsynonymous SNPs in PADI4 (padi4_89, padi4_90, and padi4_92) and SE alleles were genotyped, and serum anti-CCP levels were measured, in 311 patients with nonerosive or erosive RA. The relationships between anti-CCP levels and PADI4 haplotypes and/or SE alleles were analyzed statistically.

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