Byeong-Bae Park

Genome‐wide methylation profile of nasal polyps: relation to aspirin hypersensitivity in asthmatics

To cite this article: Cheong HS, Park S‐M, Kim M‐O, Park J‐S, Lee JY, Byun JY, Park BL, Shin HD, Park C‐S. Genome‐wide methylation profile of nasal polyps: relation to aspirin hypersensitivity in asthmatics. Allergy 2011; 66: 637–644.

Are There Any Ethnic Differences in Molecular Predictors of Erlotinib Efficacy in Advanced Non-Small Cell Lung Cancer?

Purpose: This study investigated possible molecular predictors of outcome in Korean patients with advanced non-small cell lung cancer treated with erlotinib. Experimental Design: One hundred and twenty patients received erlotinib and were followed prospectively. Ninety-two tissue samples were analyzed for epidermal growth factor receptor (EGFR) gene mutations (exons 18, 19, and 21), 88 for EGFR gene amplification by real-time PCR, and 75 for EGFR protein expression by immunohistochemistry. Results: The overall tumor response rate was 24.2% (complete response, 4; partial response, 25) with 56.7% of disease control rate. With a median follow-up of 23.6 months, the median time to progression (TTP) was 2.7 months and the median overall survival was 12.9 months. EGFR gene mutations were found in 26.1% (24 of 92), EGFR gene amplification in 40.9% (36 of 88), and EGFR protein expression in 72% (54 of 75). There was a strong association between EGFR gene mutations and gene amplification (γ = 0.241). Patients with EGFR gene mutations or gene amplification showed both better response rate (58.3% versus 16.2%, P < 0.001; 41.7% versus 17.3%, P = 0.012) and TTP (8.6 versus 2.5 months, P = 0.003; 5.8 versus 1.8 months, P < 0.001) and overall survival (not reached versus 10.8 months, P = 0.023; not reached versus 10.1 months, P = 0.033). By multivariate analysis, EGFR gene mutation was the only significant molecular predictor for TTP (hazard ratio, 0.47; 95% confidence interval, 0.25-0.89). Conclusions: Our findings indicate that EGFR gene mutation is a more predictive marker for improved TTP than EGFR gene amplification in erlotinib-treated Korean non-small cell lung cancer patients. Prospective studies from diverse ethnic backgrounds are required to determine the exact role of these molecular markers.

Association of interleukin 18 (IL18) polymorphisms with specific IgE levels to mite allergens among asthmatic patients

Background:  Allergy is regarded as a multifactorial condition. Its onset and severity are influenced by both genetic and environmental factors. Identification of genetic factors involved in asthma development and related phenotypes is a major task in understanding the genetic background of asthma. The possible involvement of IL18 polymorphisms in asthma was examined in a Korean asthma cohort.

Genetic polymorphisms in peroxisome proliferator-activated receptor gamma are associated with Type 2 diabetes mellitus and obesity in the Korean population.

Aims  We examined whether the common polymorphisms of the peroxisome proliferator‐activated receptor‐γ (PPARγ) gene are associated with Type 2 diabetes or obesity in the Korean population.

Interleukin-10 haplotype associated with total serum IgE in atopic dermatitis patients.

Background:  The genetic background of atopic dermatitis (AD) is not clearly understood. Interleukin (IL)‐10 is a powerful Th‐2 cell cytokine produced by lymphoid cells that exerts its function by inhibiting macrophage/monocyte and T‐cell lymphocyte replication and secretion of inflammatory cytokines [IL‐1, tumour necrosis factor‐α (TNFA), IL‐6, IL‐8 and IL‐12].

Identification of novel RANK polymorphisms and their putative association with low BMD among postmenopausal women

IntroductionBone mineral density (BMD) is the major factor for determining bone strength, which is closely correlated to osteoporotic fracture risk and is largely determined by multiple genetic factors. The RANK (TNFRSF11A), receptor for RANKL, is a member of the tumor necrosis factor receptor (TNFR) superfamily and plays a central role in osteoclast development.MethodsIn order to investigate the effects of RANK polymorphism on BMD and osteoporosis, we directly sequenced the RANK gene in 24 Korean individuals and identified 25 sequence variants. Eleven of these polymorphisms were selected and genotyped in a larger-scale study of postmenopausal women (n = 560). Areal BMD (g/cm2) of the anterior–posterior lumbar spine and the nondominant proximal femur were measured using dual-energy X-ray absorptiometry.Results We found that two intronic polymorphisms in the RANK gene [RANK + 34863G > A (rs12458117) and RANK + 35928insdelC (new polymorphism found in this study) in intron 6] were significantly associated with the BMD of the lumbar spine, i.e., rare alleles were significantly associated with low BMD of the lumbar spine among Korean postmenopausal women (p = 0.04 and 0.02, respectively). These polymorphisms were also associated with low BMD of proximal femur sites, including Ward’s triangle, trochanter, and total femur. Our results suggest that +34863G > A and +35928insdelC polymorphisms in RANK are possible genetic factors for low BMD in postmenopausal women.

Titin-cap (TCAP) polymorphisms associated with marbling score of beef

Marbling score (MS) is the major qualitative trait that affects carcass quality in beef cattle. In this study, we examined the association between genetic polymorphisms of the titin-cap gene (TCAP) and carcass traits in Korean native cattle (also known as Hanwoo). By direct DNA sequencing in 24 unrelated Korean cattle, we identified five sequence variants in 1.2kb of TCAP. Among them, four common polymorphic sites were selected for genotyping in the beef cattle (n=437). Pair-wise linkage analysis with four polymorphisms showed strong linkage disequilibrium (LD), and three major haplotypes (freq.>0.1) were constructed. Statistical analysis revealed that polymorphisms in intron1 (g.346G>A) and exon2 (g.592-597CTGCAG[Leu-Gln]insdel) showed significant association with marbling score (P(cor.)=0.003 and 0.02, respectively). One haplotype, ht2[C-G-G-del], also showed significant association with MS (P(cor.)=0.0004). Our findings suggest that polymorphisms in TCAP might be among the important genetic factors involved in carcass quality in beef cattle.

Association of PLXNA2 polymorphisms with vertebral fracture risk and bone mineral density in postmenopausal Korean population.

IntroductionPlexin A2 (PLXNA2) is a receptor that recognizes secreted or membrane-bound semaphorin 3A, which is implicated in neural regulation of bone metabolism.Materials and MethodsIn the present study, we identified 48 genetic polymorphisms in PLXNA2 by resequencing, and 10 single nucleotide polymorphisms (SNPs) were selected for further investigation into their potential involvement in osteoporosis in a postmenopausal population (n=560).ResultsTwo SNPs, +14G>A (Gln5Arg) and +183429C>T (Tyr1621Tyr), and Block1-ht2 were associated with risk of vertebral fracture (p=0.01–0.05), and three SNPs, +799G>A (Ala267Thr), +135391G>A, and +190531G>C, were associated with bone mineral density at various femur sites (p=0.003–0.03). Particularly, the minor allele of +14G>A was associated with a protective effect on vertebral fracture and higher lumbar bone mineral density, suggesting that +14G>A may be a useful marker for osteoporosis and its related fracture.ConclusionThese results provide, for the first time, evidence supporting the association of PLXNA2 with osteoporosis in postmenopausal women.

Associations of CD6, TNFRSF1A and IRF8 polymorphisms with risk of inflammatory demyelinating diseases

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are inflammatory autoimmune diseases that affect the central nervous system. Several genome‐wide and candidate gene studies have identified genetic polymorphisms associated with the risk of MS or NMO. In particular, two recently published studies of meta‐analysis in European‐origin populations have suggested associations of single‐nucleotide polymorphisms (SNPs) in CD6, TNFRSF1A and IRF8 with MS. The aim of our study was to assess the associations between SNPs in these three genes and the risk of inflammatory demyelinating disease (IDD) including MS and NMO. To the best of our knowledge, this is the first time such a study has been performed in an Asian population.

Commissioning of the PLS-II

After 14 years of successful operation, the Pohang Light Source (PLS) has completed PLS-II upgrade to meet the increasing demand from the growing user community. The PLS-II upgrade has increased the beam energy from 2.5 GeV to 3 GeV; the number of insertion devices has been increased by a factor of two (20 IDs); and the beam current has been increased to 400 mA from 200 mA. The beam emittance has been reduced to below 10 nm while retaining the existing PLS tunnel as well as the existing injection system. During the six months of commissioning in the latter half of 2011, we have successfully achieved 14 insertion device operations and top-up operations with 100 mA beam current and 5.8 nm beam emittance. In this paper, we report the experimental results obtained from the PLS-II commissioning.