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Aspirin-intolerant asthma (AIA) occurs from asthma exacerbation after exposure to aspirin. However, the underlying mechanisms of AIA occurrence are still unclear. The critical role of the solute carrier family 6 (neurotransmitter transporter, betaine/GABA) member 12 ( SLC6A12) gene in GABAergic transmission, which is associated with mucus production in asthma, makes it a candidate gene for AIA association study. Eight single nucleotide polymorphisms (SNPs) in SLC6A12 were genotyped in 163 aspirin-intolerant asthma (AIA) and 429 aspirin-tolerant asthma (ATA) patients of Korean ethnicity. Associations between polymorphisms of SLC6A12 and AIA were analysed using multivariate logistic analysis. Results showed that two polymorphisms and a haplotype in SLC6A12, rs499368 ( P= 0.005; Pcorr= 0.03), rs557881 (non-synonymous C10R, P= 0.007; Pcorr= 0.04), and SLC6A12_BL1_ht1 ( P= 0.009; Pcorr= 0.05) respectively, were significantly associated with AIA after multiple testing corrections. In addition, SNPs of SLC6A12 were significantly associated with the fall rate of FEV1 by aspirin provocation suggesting that SLC6A12 could affect reversibility of lung function abnormalities in AIA patients. Although these results are preliminary and future replications are needed to confirm these findings, this study showed evidence of association between variants in SLC6A12 and AIA occurrence among asthmatics in a Korean population. [ABSTRACT FROM AUTHOR]

The human chromosomal 5q31–33 region has been implicated as a susceptibility locus for several immune-mediated diseases including asthma in several populations. Recently, the extraneuronal GABAergic system has been implicated as a new link to airway obstruction in asthma. In addition, the SLC6A7 gene, which is positioned at 5q31–32 and encodes the transporter for an excitatory neurotransmitter of L-proline, has never been studied for its association with asthma. In this study, resequencing of all exon, promoter region (2 kb), and exon–intron boundary regions in the SLC6A7 gene found a total of 33 single nucleotide polymorphisms (SNPs) in 24 Korean asthmatic patients. After the initial SNP survey, a total of 17 common SNPs with minor allele frequency (MAF) over 10% were genotyped in 498 asthmatic patients and 303 normal controls. Logistic analyses revealed significant associations between genetic variants of the SLC6A7 gene and asthma (P-value up to 6.0 × 10−4; Pcorr value up to 0.009). In further regression analyses, minor alleles of intronic +11431T>C, +12213C>T and +12927A>G in linkage disequilibrium block 2 and +20113T>C in 3′UTR significantly increased the bronchodilator response in asthmatics (P-value of recessive model up to 0.008; which are not significant after multiple correction). Therefore, our findings suggest that SLC6A7 could be a susceptible gene for asthma. [ABSTRACT FROM AUTHOR]

Background: Recently, the discovery of copy number variation (CNV) led researchers to think that there are more variations of genomic DNA than initially believed. Moreover, a certain CNV region has been found to be associated with the onset of diseases. Therefore, CNV is now known as an important genomic variation in biological mechanisms. However, most CNV studies have only involved the human genome. The study of CNV involving other animals, including cattle, is severely lacking. Results: In our study of cattle, we used Illumina BovineSNP50 BeadChip (54,001 markers) to obtain each marker's signal intensity (Log R ratio) and allelic intensity (B allele frequency), which led to our discovery of 855 bovine CNVs from 265 cows. For these animals, the average number of CNVs was 3.2, average size was 149.8 kb, and median size was 171.5 kb. Taking into consideration some overlapping regions among the identified bovine CNVs, 368 unique CNV regions were detected. Among them, there were 76 common CNVRs with > 1% CNV frequency. Together, these CNVRs contained 538 genes. Heritability errors of 156 bovine pedigrees and comparative pairwise analyses were analyzed to detect 448 common deletion polymorphisms. Identified variations in this study were successfully validated using visual examination of the genoplot image, Mendelian inconsistency, another CNV identification program, and quantitative PCR. Conclusions: In this study, we describe a map of bovine CNVs and provide important resources for future bovine genome research. This result will contribute to animal breeding and protection from diseases with the aid of genomic information. [ABSTRACT FROM AUTHOR]

Background: Aspirin-intolerant asthma (AIA), which is caused by non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, causes lung inflammation and reversal bronchi reduction, leading to difficulty in breathing. Aspirin is known to affect various parts inside human body, ranging from lung to spermatogenesis. FSIP1, also known as HDS10, is a recently discovered gene that encodes fibrous sheath interacting protein 1, and is regulated by amyloid beta precursor protein (APP). Recently, it has been reported that a peptide derived from APP is cleaved by a disintegrin and metalloproteinase 33 (ADAM33), which is an asthma susceptibility gene. It has also been known that the FSIP1 gene is expressed in airway epithelium. Objectives: Aim of this study is to find out whether FSIP1 polymorphisms affect the onset of AIA in Korean population, since it is known that AIA is genetically affected by various genes. Methods: We conducted association study between 66 single nucleotide polymorphisms (SNPs) of the FSIP1 gene and AIA in total of 592 Korean subjects including 163 AIA and 429 aspirin-tolerant asthma (ATA) patients. Associations between polymorphisms of FSIP1 and AIA were analyzed with sex, smoking status, atopy, and body mass index (BMI) as covariates. Results: Initially, 18 SNPs and 4 haplotypes showed associations with AIA. However, after correcting the data for multiple testing, only one SNP showed an association with AIA (corrected P-value = 0.03, OR = 1.63, 95% CI = 1.23-2.16), showing increased susceptibility to AIA compared with that of ATA cases. Our findings suggest that FSIP1 gene might be a susceptibility gene for aspirin intolerance in asthmatics. Conclusion: Although our findings did not suggest that SNPs of FSIP1 had an effect on the reversibility of lung function abnormalities in AIA patients, they did show significant evidence of association between the variants in FSIP1 and AIA occurrence among asthmatics in a Korean population. [ABSTRACT FROM AUTHOR]

Background: Aspirin-intolerant asthma (AIA) occurs in the lower and upper airways through excessive production of leukotrienes upon administration of non-steroidal anti-inflammatory drugs (NSAIDs). One of the three symptoms of AIA is nasal polyposis, a chronic inflammatory disease that is related to the function of calcium ion in recruitment of immune cells during airway inflammation. It has been implicated that bronchodilation in the airway is related to Ca(2+) regulation. The calcium channel, voltage-dependent, gamma subunit 6 (CACNG6) gene encodes a protein that stabilizes the calcium channel. Methods: To study the associations between AIA and polymorphisms in CACNG6 gene, eight variants were genotyped in 102 AIA cases and 429 aspirin-tolerant asthma (ATA) controls. Logistic analyses were used to evaluate the associations of CACNG6 polymorphisms with AIA. Results: Statistical analyses revealed that a single nucleotide polymorphism (SNP; rs192808C > T; P = 0.0004, Pcorr = 0.0029, OR = 2.88 in co-dominant model; P = 0.0005, Pcorr = 0.0036, OR = 2.99 in dominant model) in intron and a haplotype unique to this variant (CACNG6•BL1•ht6; P = 0.003, Pcorr = 0.02, OR = 2.57 in co-dominant model, P = 0.001, Pcorr = 0.0087, OR = 2.81 in dominant model) were significantly associated with the risk of AIA. Conclusions: Our results suggest that the CACNG6 variants might be associated with the risk of AIA in a Korean population. [ABSTRACT FROM AUTHOR]

The objective of this study was to elucidate whether polymorphisms of the interleukin 23 receptor gene ( IL23R) are associated with susceptibility to systemic lupus erythematosus (SLE) in a Korean population. We recruited 602 SLE patients and 991 healthy controls. Seven single nucleotide polymorphisms (rs1004819, rs7517847, rs10489629, rs2201841, rs1343151, rs11209032, and rs1495965) were selected for genotyping among previously reported variants used in a genome-wide association study of inflammatory bowel disease. Polymorphic sites were genotyped using the TaqMan assay. The genotype distributions of IL23R polymorphisms and haplotypes were compared between the SLE patients and healthy controls using multiple logistic regression models. None of the IL23R genetic variants differed significantly between SLE patients and healthy controls, which suggests that IL23R polymorphisms play no role in the susceptibility to SLE in the Korean population. [ABSTRACT FROM AUTHOR]

The recent discovery of interleukin 23 (IL-23), its receptor, and the underlying signal transduction pathway has improved our understanding of cellular immunity. Several studies suggest that IL-23 is an essential promoter of chronic joint inflammation. In this report, we assess the possible association of interleukin 23 receptor (IL23R) polymorphisms and haplotypes with rheumatoid arthritis (RA). The study was conducted on 1,204 RA patients and 979 healthy controls. Seven polymorphisms were selected from previous IBD reports. The seven SNPs (rs1004819, rs7517847, rs10489629, rs2201841, rs1343151, rs11209032 and rs1495965) were genotyped using the TaqMan assay. Comparison of RA and control subjects revealed no statistically significant differences in the distribution of the IL23R genotypes and haplotypes. Our results clearly indicate that IL23R gene polymorphisms do not play a significant role in susceptibility to RA in the Korean population. Accordingly, we conclude that IL23R gene polymorphisms cannot be applied as an effective genetic marker for RA susceptibility. [ABSTRACT FROM AUTHOR]

The article discusses the study which examines the effects of polymorphism on the transcription of interleukin 17 receptor B (IL-17RB) isoforms. The study used 654 asthmatics or 356 healthy control subjects who underwent screening for polymorphism in IL-17RB by single-base extension where B-cells were measured by reverse transcription polymerase chain reaction. IT shows that the activation of IL-17RB intensifies allergic-type inflammatory responses by inducing Jun kinase and protein kinase.

Background: Marbling score (MS) is the major quantitative trait that affects carcass quality in beef cattle. In this study, we examined the association between genetic polymorphisms of the micromolar calcium-activated neutral protease gene (micro-calpain, CAPN1) and carcass traits in Korean cattle (also known as Hanwoo). Results: By direct DNA sequencing in 24 unrelated Korean cattle, we identified 39 sequence variants within exons and their flanking regions in CAPN1. Among them, 12 common polymorphic sites were selected for genotyping in the beef cattle (n = 421). Statistical analysis revealed that a polymorphism in the 3'UTR (c.2151*479C>T) showed significant association with MS (Pcor. = 0.02). Conclusion: Our findings suggest that polymorphisms in CAPN1 might be one of the important genetic factors involved in carcass quality in beef cattle, although it could be false positive association. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between genetic variation in the renin-angiotensin system and the effect of 12-week endurance training in Korean women. Materials and Methods: Seventeen women who participated in an endurance training program for 12 weeks were genotyped for the angiotensinogen M235T polymorphism, angiotensin II type 1 receptor A1166C polymorphism, angiotensin-converting enzyme (ACE) T-3892C polymorphism, and angiotensin II type 2 receptor C3123A polymorphism. The following clinical parameters were measured before and after the endurance training program: blood pressure, body composition, ventilatory response, total cholesterol, triglyceride, and glucose. Results: Of the genetic markers investigated, the frequency of the T allele for the ACE T-3892C polymorphism was significantly associated with the response in body mass index and VO2max after 12 weeks of endurance training (p< 0.05). None of the other polymorphisms were significantly associated with the effect of training. Conclusion: The significant association between ACE T-3892C and the change in body mass index and VO2max in Korean women are attributed to training, suggesting that this genetic variation is a useful genetic marker for clarifying the interindividual response to endurance training. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]