A possible association between ZNRD1 and aspirin-induced airway bronchoconstriction in a Korean population.

BACKGROUND: The etiology of aspirin-exacerbated respiratory disease (AERD) has been attributed to the combination of environmental and genetic risk factors. Although widely investigated in various diseases associated with immune dysfunction, the human zinc ribbon domain containing 1 (ZNRD1) gene is thought to play a role in the pathogenesis of AERD by altering the mechanisms involved in disease development. METHODS: We selected 6 single-nucleotide polymorphisms (SNPs) for genotyping from the International HapMap database in order to analyze the association between polymorphisms in ZNRD1 and AERD in a Korean asthma cohort. Genotyping was carried out using the TaqMan assay, and differences in genotype frequency distributions were analyzed using logistic regression models. RESULTS: Nominal associations were found between ZNRD1 rs1150740 and risk ofAERD via codominant and dominant genetic inheritance (P=.03; odds ratio, 1.14 [1.14-10.16]). The same polymorphism was found to be significantly associated with a decrease in forced expiratory volume in the first second of expiration, an important diagnostic marker of AERD, even after multiple testing corrections (P=.006, P(corr)=.03 in codominant and dominant models). CONCLUSIONS: These preliminary findings suggest a possible relationship between ZNRD1 and aspirin-induced respiratory dysfunctions in a Korean population and provide essential information on the etiology of AERD.

Variations in the STK10 gene and possible associations with aspirin-intolerant asthma in a Korean population.

BACKGROUND AND OBJECTIVE: Lymphocyte-oriented kinase deficiency encoded by the serine/threonine kinase 10 (STK10) gene correlates with the intracellular adhesion molecule 1 (ICAM-1)/lymphocyte function associated antigen 1 (LFA-1) complex in aspirin hypersensitivity. This study investigated the association between single nucleotide polymorphisms (SNPs) of STK10 and aspirin-intolerant asthma (AIA). METHODS: A total of 54 SNPs were genotyped in 163 AIA patients and 429 aspirin-tolerant asthma (ATA) controls. RESULTS: Logistic regression revealed that a synonymous variant (rs2306961G>A) had the most significant association with AIA (P = .008 under the codominant model; P = .004 under the dominant model), suggesting that tissue-specific codon usage between Lys_TTT and Lys_CTT could play a role in regulating expression of STK10 in airway epithelium. Haplotype analysis revealed that 4 haplotypes, including STK10_BL4-ht1, which is unique to rs2306961G>A, were significantly associated with aspirin hypersensitivity in asthmatics (P < .05). CONCLUSIONS: Although replications in independent cohorts and further functional evaluations are needed, our preliminary findings suggest that STK10 polymorphisms might be susceptible genetic markers of AIA and that gene expression could be mediated by tissue-specific codon usage.

Neuregulin 3 does not confer risk for schizophrenia and smooth pursuit eye movement abnormality in a Korean population.

Located on chromosome 10q22-q23, the human neuregulin3 (NRG3) is considered to be a strong positional and functional candidate gene for schizophrenia pathogenesis. Several case-control studies examining the association of polymorphisms in NRG3 with schizophrenia and/or related traits such as delusion have been reported recently in cohorts of Han Chinese, Ashkenazi Jews, Australians and white Americans of Western European ancestry. Thus, this study aimed to comprehensively investigate the association of NRG3 genetic variations with the risk of schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean population. Using TaqMan assay, six single-nucleotide polymorphisms (SNPs) in the intronic region of NRG3 were genotyped and two major haplotypes were identified in 435 patients with schizophrenia as cases and 393 unrelated healthy individuals as controls. A total of 113 schizophrenia patients underwent an eye tracking task, and degree of SPEM abnormality was measured using the logarithmic values of the signal/noise (Ln S/N) ratio. Differences in frequency distributions were analyzed using logistic and regression models following various modes of genetic inheritance and controlling for age and sex as covariates. Subsequent analysis revealed that the frequency distributions of NRG3 polymorphisms and haplotypes were similar between schizophrenia patients and healthy controls of Korean ethnicity. Furthermore, no significant differences were observed between the genetic variants tested for SPEM abnormality. By elucidating a lack of association in a Korean population, findings from this study may contribute to the understanding of the genetic etiology focusing on the role of NRG3 in schizophrenia pathogenesis.