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Purpose Melanocortin 3 Receptor (MC3R) is one of the families of seven-transmembrane G-protein-coupled receptors, and a recent study showed that MCR3 promoter polymorphism was significantly associated with the susceptibility of tuberculosis (TB) in South African population. Methods We analyzed six MC3R polymorphisms to examine the genetic effects on the risk of pulmonary TB in Korean subjects by using TaqMan assays and case-control analyses. Results Using statistical analyses, one common promoter polymorphism (MC3Rrs11575886 T > C) was found to be associated with an increased risk of pulmonary TB. The frequency of the C-bearing genotype of rs11575886 was higher in pulmonary TB patients than in normal controls (p = 0.03, OR = 1.46) although the significance was not retained after correction. In silico analysis for the difference of transcription binding factor (TF), motif between C and T allele demonstrated that the TF motif and its threshold scores of C allele were lower than those of T allele. Conclusions The C allele of rs11575886 could be a risk allele for the pulmonary TB by affecting the binding of TF. Our findings suggest that polymorphisms in MC3R might be one of genetic factors for the risk of pulmonary TB development in Korean subjects. Electronic supplementary material The online version of this article (doi:10.1007/s00408-014-9625-2) contains supplementary material, which is available to authorized users., Author(s): Byung Lae Park[sup.1] , Lyoung Hyo Kim[sup.1] [sup.2] , Suhg Namgoong[sup.1] [sup.2] , Ji On Kim[sup.1] [sup.2] , Jason Yongha Kim[sup.2] , Hun Soo Chang[sup.3] [sup.4] [sup.5] , Jong [...]

BACKGROUND:The functional role of the human diffuse panbronchiolitis critical region 1 (DPCR1) gene, located in the major histocompatibility complex class I, has not been widely investigated. However, this gene is a well known genetic marker for diffuse panbronchiolitis, a disease affecting human respiratory bronchioles. In this study we explored the association between polymorphisms in DPCR1 and aspirin-exacerbated respiratory disease (AERD), an asthma phenotype. METHODS: Genotyping of 6 polymorphisms was carried out in a total of 189 Korean asthmatic patients stratified into 93 AERD cases and 96 aspirin tolerant asthma controls. Subjects who exhibited significant decrease of FEV1 by aspirin provocation were identified as AERD subjects. Logistic and regression analyses were performed to investigate the association between DPCR1 polymorphisms and the risk of AERD as well as FEV1 decline. RESULTS: Initial analysis revealed significant association of rs2517449 with AERD, with a P value of .03 via a recessive model; however, the association signal disappeared after multiple testing corrections. In addition, rs2517449 and rs2240804 also showed association signals with decline of FEV1 after aspirin provocation (P = .007 and .03, respectively, in a recessive model). After testing for multiple comparisons, only the association signal from rs2517449 was retained (Pcorr = .04), while other polymorphisms showed no associations with the risk of AERD and FEV1 decline. CONCLUSIONS: Our results show that polymorphisms in DPCR1 are not associated with the risk of AERD. [ABSTRACT FROM AUTHOR]

Background. The discoidin domain receptor tyrosine kinase 1 (DDR1) is positioned within the major histocompatibility complex (MHC) region which plays an important role in the immune system. In addition, DDR1 has been elucidated to be downregulated during the epithelial-mesenchymal transition of bronchial epithelium. Objective. To investigate the potential genetic associations between DDR1 and aspirin-exacerbated respiratory disease (AERD), this study conducted association studies of DDR1 single nucleotide polymorphisms (SNPs) with AERD and the obstructive symptom of forced expiratory volume in 1 s (FEV1) decline after aspirin provocation. Methods. Nine common SNPs were genotyped in 93 AERD patients and 96 aspirin-tolerant asthma (ATA) controls. The genotype distributions of all loci were in Hardy-Weinberg equilibrium (HWE; p > .05). Results. In the results of logistic analyses using age, sex, smoking status, and atopy as covariates, DDR1 rs1264320 in the intronic region showed a potent association signal with FEV1 decline by aspirin provocation in asthmatics of this study even after corrections for multiple testing (p = .003 and corrected p = .01). However, the variants of DDR1 were not significantly associated with the AERD development (corrected p > .05). On further comparison of FEV1 decline by aspirin provocation between AERD and ATA, the variant rs1264320 was found to be associated with the FEV1 decline of ATA rather than AERD. Conclusion. Despite the need for further functional evaluations and replications, we conclude that DDR1 polymorphisms are not likely to contribute to predispositions of AERD, but may be potentially associated with FEV1 decline by aspirin provocation in asthmatics. [ABSTRACT FROM AUTHOR]

Schizophrenia is a serious mental disorder that is affected by genetic and environmental factors. As the disease has a high heritability rate, genetic studies identifying candidate genes for schizophrenia have been conducted in various populations. The gene for human Ran‑binding protein 9 (RANBP9) is a newly discovered candidate gene for schizophrenia. As RANBP9 is a small guanosine‑5'‑triphosphate‑binding protein that interacts with the disrupted in schizophrenia 1 protein, it is considered to be an important molecule in the pathogenesis of schizophrenia. However, to date, no study has examined the possible association between the genetic variations of RANBP9 and the risk of schizophrenia. In the present study, it was hypothesized that RANBP9 variations may influence the risk of schizophrenia. In order to investigate the association between RANBP9 polymorphisms and the risk of schizophrenia and smooth pursuit eye movement (SPEM) abnormalities, a case‑control association analysis was performed. Using a TaqMan assay, five single‑nucleotide polymorphisms and an insertion/deletion variation within the start codon region of RANBP9 were genotyped. Five major haplotypes were identified in 449 patients with schizophrenia and 393 unrelated healthy individuals as controls (total, n=842). However, the association analyses revealed no associations between all genetic variants and schizophrenia and SPEM abnormality. To the best of our knowledge, this is the first study to investigate an association between RANBP9 polymorphisms and schizophrenia and SPEM abnormality. The findings of allele frequencies and association results in this study may aid in further genetic etiological studies in schizophrenia in various populations.

The tyrosine-protein kinase Tec (TEC) is a member of non-receptor tyrosine kinases and has critical roles in cell signaling transmission, calcium mobilization, gene expression, and transformation. TEC is also involved in various immune responses, such as mast cell activation. Therefore, we hypothesized that TEC polymorphisms might be involved in aspirin-exacerbated respiratory disease (AERD) pathogenesis. We genotyped 38 TEC single nucleotide polymorphisms in a total of 592 subjects, which comprised 163 AERD cases and 429 aspirin-tolerant asthma controls. Logistic regression analysis was performed to examine the associations between TEC polymorphisms and the risk of AERD in a Korean population. The results revealed that TEC polymorphisms and major haplotypes were not associated with the risk of AERD. In another regression analysis for the fall rate of forced expiratory volume in 1 second (FEV1) by aspirin provocation, two variations (rs7664091 and rs12500534) and one haplotype (TEC_BL2_ht4) showed nominal associations with FEV1 decline (p = 0.03-0.04). However, the association signals were not retained after performing corrections for multiple testing. Despite TEC playing an important role in immune responses, the results from the present study suggest that TEC polymorphisms do not affect AERD susceptibility. Findings from the present study might contribute to the genetic etiology of AERD pathogenesis.

Multiple sclerosis (MS) and neuromyelitis optica (NMO), which are referred to as inflammatory demyelinating diseases (IDDs), are autoimmune diseases affecting the central nervous system. Interleukin‑7 receptor (IL7R) encodes for a receptor protein that is important in the development of immune cells. Several studies have reported significant associations between IL7R polymorphisms and MS. The aim of the present study was to investigate a possible association between IL7R polymorphisms and IDDs such as MS and NMO. Thirteen single nucleotide polymorphisms (SNPs) were selected based on their linkage disequilibrium (LD), minor allele frequency (MAF) and location, and were genotyped in 178 IDD patients and 237 healthy controls. The association of SNPs with IDD risk was analyzed by logistic regression. A meta‑analysis on the association between rs6897932 and the risk of MS was also performed. Statistical analyses revealed that a common SNP, rs6897932, was marginally associated with IDD in a recessive model (P=0.003, Pcor.=0.03), which had shown significant associations with MS in previous studies. The results replicated the significant association found between rs6897932 and IDD. In addition, the meta‑analysis of rs6897932 clearly demonstrates a higher magnitude of risk in Asian populations than in Caucasian populations. Although there are certain limitations to our study, the results indicate that the genetic variation of IL7R may be associated with IDDs such as MS and NMO in the population studied.

Purpose: Aspirin exacerbated respiratory disease (AERD) results in a severe asthma attack after aspirin ingestion in asthmatics. The filamin A interacting protein 1 (FILIP1) may play a crucial role in AERD pathogenesis by mediating T cell activation and membrane rearrangement. We investigated the association of FILIP1 variations with AERD and the fall rate of forced expiratory volume in one second (FEV1)., Methods: A total of 34 common FILIP1 single nucleotide polymorphisms (SNPs) were genotyped in 592 Korean asthmatic subjects that included 163 AERD patients and 429 aspirin-tolerant asthma (ATA) controls., Results: This study found that 5 SNPs (P=0.006-0.01) and 2 haplotypes (P=0.01-0.03) of FILIP1 showed nominal signals; however, corrections for the multiple testing revealed no significant associations with the development of AERD (P(corr)>0.05). In addition, association analysis of the genetic variants with the fall rate of FEV1, an important diagnostic marker of AERD, revealed no significant evidence (P(corr)>0.05)., Conclusions: Although further replications and functional evaluations are needed, our preliminary findings suggest that genetic variants of FILIP1 might be not associated with the onset of AERD.

Objective: This study was conducted to find the possible association between CD226 polymorphisms and inflammatory demyelinating diseases in Korean population., Methods: A total of 14 CD226 SNPs were selected based on their linkage disequilibrium, minor allele frequency, and location. Then, the SNPs were genotyped in 178 IDD patients and 237 healthy controls. Subsequently, we conducted logistic analysis to find possible associations, Results: Statistical analyses revealed only a marginal signal for a common SNP rs1788229 with inflammatory demyelinating disease (p=0.05), while other SNPs failed to show associations with any diseases. However, the significance of rs1788229 disappeared after a multiple testing correction of the data (p>0.05). Interestingly, rs763361, which showed significant associations with multiple sclerosis in several previous studies, did not show any association at all., Conclusions: While prior studies have found CD226 polymorphisms to be significantly associated with inflammatory demyelinating diseases, our results indicate the CD226 polymorphisms to be not associated with the diseases in Korean population. However, our results suggest that the causal genes for inflammatory demyelinating diseases may vary depending on the population.

Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome that is characterized by nasal polyposis, general symptoms of asthma and sensitive response to non-steroidal anti-inflammatory drugs (NSAIDs). Although the exact function of tripartite motif-containing 26 (TRIM26) still remains unknown, the gene functions in the immune response. Thus, we hypothesized that TRIM26 polymorphisms may affect aspirin-induced bronchospasm and explored whether the gene can be a marker for diagnosis of AERD. To investigate our hypothesis that TRIM26 may serve as a genetic marker for diagnosis of AERD, this study focused on demonstrating the associations between single nucleotide polymorphisms (SNPs) of the TRIM26 gene and AERD. We genotyped 18 polymorphisms of TRIM26 in a total of 189 asthmatics and examined their associations with the risk of AERD. We performed logistic analysis for obtaining P-values and regression analysis for demonstrating an association between the phenotype with FEV1 and the genotype. We observed no associations between polymorphisms in TRIM26 and the risk of AERD in both logistic and regression analyses. Although our results reveal a lack of association, the suggested functional role of TRIM26 makes it a putative candidate gene for AERD. Thus, replications in other populations using larger samples may provide valuable information for AERD etiology.

Background: Aspirin-intolerant asthma (AIA), as a clinical syndrome caused by aspirin, is characterized by lung inflammation and reversible bronchoconstriction. Recently, the altered trafficking and diminished airway reactivity have been implicated in allergic airway remodeling. The stromal membrane-associated protein 1-like (SMAP1L) exerts common and distinct functions in vesicle trafficking including endocytosis. The disturbance of pulmonary surfactant synthesis has been elucidated to be associated with asthma experimentally. Moreover, in alveolar type II (ATII) cells that synthesize pulmonary surfactant, alterations of clathrin-dependent endocytosis cause disturbance at the surfactant function, suggesting that SMAP1L, which directly interacts with clathrin, could be associated with asthma and related phenotypes., Objective: To verify our hypothesis that SMAP1L could play a role in the development of AIA, this study investigated associations between single-nucleotide polymorphisms (SNPs) of the SMAP1L gene and AIA., Methods: We conducted an association study between 19 SNPs of the SMAP1L gene and AIA in a total of 592 Korean subjects including 163 AIA and 429 aspirin-tolerant asthma (ATA) patients. Associations between polymorphisms of SMAP1L and AIA were analyzed with sex, smoking status, atopy, and body mass index as covariates., Results: Logistic analyses revealed that three common polymorphisms, rs2982510, rs2294752, and rs446738, were putatively associated with the increased susceptibility to AIA (p = .003, p(corr) = .004, OR = 0.24, 95% CI = 0.09-0.62 for rs2982510 and rs2294752; p = .008, p(corr) = .03, OR = 0.44, 95% CI = 0.24-0.80 for rs446738, in the recessive model). In addition, rs2982510 and rs2294752 were significantly associated with the fall of forced expiratory volume in 1 s (FEV₁) by aspirin provocation (p = .001, p(corr) = .04 in the recessive model for both SNPs)., Conclusions: Our findings suggest that SMAP1L might be a susceptible gene to AIA, providing a new strategy for the control of aspirin intolerance.