Association between colony-stimulating factor 1 receptor gene polymorphisms and asthma risk

Shin, Eun Kyong,Lee, Shin-Hwa,Cho, Sung-Hwan,Jung, Seok,Yoon, Sang Hyuk,Park, Sung Woo,Park, Jong Sook,Uh, Soo Taek,Kim, Yang Ki,Kim, Yong Hoon,Choi, Jae-Sung,Park, Byung-Lae,Shin, Hyoung Doo,Park, Ch Springer-Verlag 2010 HUMAN GENETICS Vol.128 No.3

<P>Colony-stimulating factor 1 receptor (<I>CSF1R</I>) is expressed in monocytes/macrophages and dendritic cells. These cells play important roles in the innate immune response, which is regarded as an important aspect of asthma development. Genetic alterations in the <I>CSF1R</I> gene may contribute to the development of asthma. We investigated whether <I>CSF1R</I> gene polymorphisms were associated with the risk of asthma. Through direct DNA sequencing of the <I>CSF1R</I> gene, we identified 28 single nucleotide polymorphisms (SNPs) and genotyped them in 303 normal controls and 498 asthmatic patients. Expression of <I>CSF1R</I> protein and mRNA were measured on CD14-positive monocytes and neutrophils in peripheral blood of asthmatic patients using flow cytometry and real-time PCR. Among the 28 polymorphisms, two intronic polymorphism (+<I>20511C</I>><I>T</I> and +<I>22693T</I>><I>C</I>) were associated with the risk of asthma by logistic regression analysis. The frequencies of the minor allele at <I>CSF1R</I> +<I>20511C</I>><I>T</I> and +<I>22693T</I>><I>C</I> were higher in asthmatic subjects than in normal controls (4.6 vs. 7.7%, <I>p</I> = 0.001 in co-dominant and dominant models; 16.4 vs. 25.8%, <I>p</I> = 0.0006 in a recessive model). <I>CSF1R</I> mRNA levels in neutrophils of the asthmatic patients having the +<I>22693CC</I> allele were higher than in those having the +<I>22693TT</I> allele (<I>p</I> = 0.026). Asthmatic patients with the +<I>22693CC</I> allele also showed significantly higher <I>CSF1R</I> expression on CD14-positive monocytes and neutrophils than did those with the +<I>22693TT</I> allele (<I>p</I> = 0.045 and <I>p</I> = 0.044). The +<I>20511C</I>><I>T</I> SNP had no association with <I>CSF1R</I> mRNA or protein expression. In conclusion, the minor allele at <I>CSF1R</I> +<I>22693T</I>>C may have a susceptibility effect in the development of asthma, via increased <I>CSF1R</I> protein and mRNA expression in inflammatory cells.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1007/s00439-010-0850-3) contains supplementary material, which is available to authorized users.</P>

Association of peroxisome proliferator-activated receptor-gamma gene polymorphisms with the development of asthma

Oh, Sun-Hee,Park, Se-Min,Lee, Yoo Hoon,Cha, Ji Yeon,Lee, Ji-Yeon,Shin, Eun Kyong,Park, Jong-Sook,Park, Byeong-Lae,Shin, Hyoung Doo,Park, Choon-Sik Elsevier 2009 Respiratory medicine Vol.103 No.7

<P><B>Summary</B></P><P><B>Background</B></P><P>The peroxisome proliferator-activated receptors (PPAR) are the nuclear hormone receptor superfamily of ligand-activated transcriptional factors. PPAR-gamma (PPARG) activation downregulates production of Th2 type cytokines and <I>eosinophil</I> function. Additionally, treatment with a synthetic PPARG ligand can reduce lung inflammation and IFN-gamma, IL-4, and IL-2 production in experimental allergic asthma. In patients with asthma, <I>PPARG</I> gene expression is known to be associated with the airway inflammatory and remodeling responses. Thus, genetic variants of <I>PPARG</I> may be associated with the development of asthma.</P><P><B>Methods</B></P><P>We genotyped two single nucleotide polymorphisms on the <I>PPARG</I> gene, +<I>34C</I>><I>G</I> (Pro12Ala) and +<I>82466C</I>><I>T</I> (His449His), in Korean subjects (839 subjects with asthma and 449 normal controls).</P><P><B>Results</B></P><P>Association analysis using logistic regression analysis showed that +<I>82466C</I>><I>T</I> and haplotypes 1(CC) and 2(CT) were associated with the development of asthma (<I>p</I>=0.01–0.04). The frequency of <I>PPARG</I>-<I>ht2</I> was significantly lower in the patients with asthma compared to the normal controls in codominant and dominant models (<I>p</I>=0.01, <I>p</I><SUB>corr</SUB>=0.03 and <I>p</I>=0.02, <I>p</I><SUB>corr</SUB>=0.03, respectively). Conversely, the frequency of <I>PPARG</I>-<I>ht1</I> was significantly higher in the patients with asthma compared to the normal controls in the codominant model [<I>p</I>=0.04, OR: 1.27 (1.01–1.6)]. In addition, the rare allele frequency of +<I>82466C</I>><I>T</I> was significantly lower in patients with asthma in comparison to normal controls in the codominant model (OR: 0.78, <I>p</I>=0.04). Thus, polymorphism of the <I>PPARG</I> gene may be linked to an increased risk of asthma development.</P>

Dietary evaluation of a low-iodine diet in Korean thyroid cancer patients preparing for radioactive iodine therapy in an iodine-rich region

Dal Lae Ju,Young Joo Park,Hee-Young Paik,Min-Ji Kim,Seonyeong Park,Kyong Yeun Jung,Tae Hyuk Kim,Hun Sung Choi,Yoon Ju Song 한국영양학회 2016 Nutrition Research and Practice Vol.10 No.2

BACKGROUND/OBJECTIVES: Despite the importance of a low-iodine diet (LID) for thyroid cancer patients preparing for radioactive iodine (RAI) therapy, few studies have evaluated dietary intake during LID. This study evaluated the amount of dietary iodine intake and its major food sources during a typical diet and during LID periods for thyroid cancer patients preparing for RAI therapy, and examined how the type of nutrition education of LID affects iodine intake. SUBJECTS/METHODS: A total of 92 differentiated thyroid cancer patients with total thyroidectomy were enrolled from Seoul National University Hospital. All subjects completed three days of dietary records during usual and low-iodine diets before 131I administration. RESULTS: The median iodine intake was 290 ㎍/day on the usual diet and 63.2 ㎍/day on the LID. The major food groups during the usual diet were seaweed, salted vegetables, fish, milk, and dairy products and the consumption of these foods decreased significantly during LID. The mean energy intake on the LID was 1,325 ㎉, which was 446 ㎉ lower than on the usual diet (1,771 ㎉). By avoiding iodine, the intake of most other nutrients, including sodium, was significantly reduced during LID (P < 0.005). Regarding nutritional education, intensive education was more effective than a simple education at reducing iodine intake. CONCLUSION: Iodine intake for thyroid cancer patients was significantly reduced during LID and was within the recommended amount. However, the intake of most other nutrients and calories was also reduced. Future studies are needed to develop a practical dietary protocol for a LID in Korean patients.

암 환자의 임상영양치료를 위한 임상영양사의 직무분석과 직무표준 개발

최수경 ( Soo Kyong Choi ),위경애 ( Gyung Ah Wie ),이송미 ( Song Mi Lee ),김은미 ( Eun Mi Kim ),박미선 ( Mi Sun Park ),손정민 ( Cheong Min Sohn ),우미혜 ( Mi Hye Woo ),주달래 ( Dal Lae Ju ),차진아 ( Jin A Cha ),서정숙 ( Jung Sook S 대한영양사협회 2015 대한영양사협회 학술지 Vol.21 No.2

The present study was conducted to provide the basis for improvement of clinical nutrition services through development of job standards of clinical dietitian for the clinical nutrition therapy to cancer patients in hospitals. Developing A Curriculum (DACUM) method was used for job analysis and development of job standards for clinical dietitians for cancer care. Based on DACUM analysis, information about duties, tasks, and task elements of clinical dietitians for cancer care was collected. Developed job standards were applied to clinical nutrition care for cancer patients in hospitals for evaluation. Based on DACUM analysis, consultations from professionals, and field application tests, the final job standards were composed of four duties, 18 tasks, and 56 task elements. The duties consisted of nutritional assessment, nutrition diagnosis, nutrition intervention, and nutrition monitoringㆍevaluation. For cancer nutrition care, 109 work activities were developed. They were composed of 75 basic and 34 recommended work activities. The application of developed job standards for clinical dietitians for cancer care at 10 hospitals showed a performance rate of 72.3%. In conclusion, job standards for clinical dietitians for cancer care developed in this study might be effectively used as guidelines for providing clinical nutrition services for cancer patients in hospitals.

Association of variations in TPH1 and HTR2B with gestational weight gain and measures of obesity.

Kwak, Soo Heon,Park, Byoung Lae,Kim, Hail,German, Michael S,Go, Min Jin,Jung, Hye Seung,Koo, Bo Kyong,Cho, Young Min,Choi, Sung Hee,Cho, Yoon Shin,Shin, Hyoung Doo,Jang, Hak C,Park, Kyong Soo NAASO, the Obesity Society 2012 Obesity Vol.20 No.1

<P>Serotonin is involved in appetite regulation and energy homeostasis. Recently, it has been reported that 5-hydroxytryptamine receptor 2B (Htr2b) and tryptophan hydroxylase 1 (Tph1) play major role in β-cell proliferation in mouse during pregnancy. We investigated the genetic association of HTR2B and TPH1 with risk of gestational diabetes mellitus (GDM) and measures of obesity, in 869 Korean GDM women and carefully selected 632 nondiabetic control subjects. Six single-nucleotide polymorphisms (SNPs) in HTR2B and ten SNPs in TPH1 were selected for genotyping according to their tagging status. Genetic variants in HTR2B and TPH1 were not associated with the risk of GDM. In GDM women, SNPs of TPH1 were significantly associated with weight gain during pregnancy. In nondiabetic controls, SNPs of TPH1 were associated with waist circumference and BMI. We also found that a variant of TPH1 (rs623580) was associated with BMI in a genome-wide association study comprised of 8,842 subjects. Although genetic variants in HTR2B and TPH1 were not associated with risk of GDM, we found significant association of these variants with measures of obesity. However, further replication studies in a different population are required to confirm our findings.</P>

만성 신부전을 동반한 Laurence Moon-Bardet Biedl 증후군 1례

박래경,이동환,문철,김은미,Park Lae Kyong,Lee Dong Hwan,Moon Chul,Kim Eun Mi 대한소아신장학회 1998 Childhood kidney diseases Vol.2 No.2

The Laurence Moon-Bardet Biedl syndrome is characterized by obesity, mental retardation, visual impairment with retinitis pigmentosa, polydactyly, hypogonadism and renal manifestations. We experienced an 11 years old female with Laurence Moon-Baret Biedl syndrome associated chronic renal failure. She was diagnosed to have LMB syndrom according to the clinical manifestations of polydactyly on hands and feet, mental retardation, obesity, retinitis pigmentosa and chronic renal failure. She is on maintenance hemodialysis now.

B형 간염의 만성화 및 간세포암종 발생과 Interleukin-12 유전자 다형성

박진선 ( Jin Sun Park ),정재연 ( Jae Youn Cheong ),강준구 ( Joon Koo Kang ),조진희 ( Jin Hee Cho ),유수경 ( Su Kyong Yu ),신형두 ( Hyoung Doo Shin ),박병래 ( Byung Lae Park ),조성원 ( Sung Won Cho ) 대한소화기학회 2007 대한소화기학회지 Vol.50 No.5

목적: B형 간염바이러스(hepatitis B virus, HBV) 감염은 다양한 임상 경과를 갖는다. HBV 감염의 자연경과의 다양성의 원인으로 유전자 다형성을 포함한 숙주 요인을 들 수 있으며, 사이토카인은 숙주 면역능에 중요한 역할을 한다. 이번 연구는 HBV 감염 후의 자연 경과와 간세포암종 발생에서 interleukin (IL)-12A 유전자 다형성(single neucleotide polymorphisms, SNP)과의 상관성을 알아보고자 하였다. 대상 및 방법: 2002년 3월부터 2004년 12월까지 외래를 내원한 HBV 만성화군 730명과 HBV 감염 후 자연 회복된 HBV 제거군 320명을 포함하여 총 1,050명을 대상으로 하였다. B형 간염의 만성화와 IL-12A의 유전자 다형성과의 관련성을 조사하기 위하여, HBV 만성화군과 HBV 제거군의 IL-12A SNP 및 haplotype에 따른 차이를 비교 분석하였고, 간세포암종 발생과 IL-12A의 유전자 다형성과의 관련성을 조사하기 위하여, HBV 만성화군을 간세포암종군과 비간세포암종군으로 나누어 IL-12A SNP 및 haplotype에 따른 차이를 비교 분석하였다. 결과: IL-12A의 SNP는 IL-12A 유전자 번역 시작 부위로부터 +6400, +6624, +7003 부위에서 조사하였다. 대상 환자를 HBV 만성화군과 HBV 제거군으로 분류하고, IL-12A SNP와 HBV 만성화와의 관련성을 조사한 결과 IL-12A exon 7 +6400 및 +6624 두 부위 및 3` UTR +7003 한 부위의 SNP는 HBV 만성화군과 HBV 제거군 간에 유의한 차이를 보이지 않았다. 또한 +6400/+6624/+7003 haplotype에 따른 HBV 만성화 관련성 조사에서도 양 군 간에 유의한 차이점은 관찰되지 않았다. IL-12A SNP와 간세포암종과의 관련성을 조사한 결과 각각의 SNP 및 +6400/ +6624/+7003 haplotype에 따른 HBV 감염 후 간세포암종 발생과의 연관성도 관찰되지 않았다. 결론: IL-12A SNP 및 haplotype은 HBV 간염 진행 및 간세포암종 진행과는 무관함을 알 수 있었다. HBV 감염의 자연 경과에서 숙주의 유전적인 인자의 중요성을 인지하고, 향후 환자의 유전 소인에 대한 연구가 더 진행되어야 할 것으로 판단한다. Background/Aims: Infection with hepatitis B virus (HBV) may result in various conditions. Natural course of HBV infection is influenced by various host immune factors and cytokines play a crucial role in host immune defense. This study was undertaken to investigate the association between HBV persistence and development of hepatocelluar carcinoma (HCC) and single nucleotide polymorphisms (SNPs) of interleukin (IL)-12A. Methods: Between March 2002 and December 2004, seven hundred thirty Korean patients with HBV infection and 320 healthy individuals who recovered from HBV infection were enrolled. We assessed polymorphisms and haplotype in IL-12A, and the genotype distributions of the HBV clearance and persistence groups were compared in order to investigate the association between HBV persistence and SNPs of IL-12A. Moreover, the genotypic distributions between patients with HCC and without HCC were compared to investigate the association between the development of HCC and SNPs of IL-12A. Results: We asssesed the SNPs of IL-12A at position +6400, +6624 and +7003. On the basis of logistic regression analysis, no statistically significant association with HBV persistence was observed with IL-12A exon 7 +6400, +6624, 3` UTR +7003 SNP and haplotype of IL-12A +6400/+6624/+7003. Furthermore, no statistically significant association of HCC development with IL-12A exon 7 +6400, +6624, 3` UTR +7003 SNP and haplotype of IL-12A +6400/+6624/+7003 was observed. Conclusions: These results suggest that SNPs and haplotype of IL-12A are not associated with HBV persistence and development of HCC. Further studies are needed to identify the host genetic factors in immune defense including cytokine gene polymorphisms of both IL-12A and IL-12B. (Korean J Gastroenterol 2007;50:313-318)

Implication of Genetic Variants Near <i>TCF7L2</i> , <i>SLC30A8</i> , <i>HHEX</i> , <i>CDKAL1</i> , <i>CDKN2A/B</i> , <i>IGF2BP2</i> , and <i>FTO</i> in Type 2 Diabetes and Obesity in 6,719 Asians

Ng, Maggie C.Y.,Park, Kyong Soo,Oh, Bermseok,Tam, Claudia H.T.,Cho, Young Min,Shin, Hyoung Doo,Lam, Vincent K.L.,Ma, Ronald C.W.,So, Wing Yee,Cho, Yoon Shin,Kim, Hyung-Lae,Lee, Hong Kyu,Chan, Juliana American Diabetes Association 2008 Diabetes Vol.57 No.8

<P><B>OBJECTIVE—</B> Recent genome-wide association studies have identified six novel genes for type 2 diabetes and obesity and confirmed <I>TCF7L2</I> as the major type 2 diabetes gene to date in Europeans. However, the implications of these genes in Asians are unclear.</P><P><B>RESEARCH DESIGN AND METHODS—</B> We studied 13 associated single nucleotide polymorphisms from these genes in 3,041 patients with type 2 diabetes and 3,678 control subjects of Asian ancestry from Hong Kong and Korea.</P><P><B>RESULTS—</B> We confirmed the associations of <I>TCF7L2</I>, <I>SLC30A8</I>, <I>HHEX</I>, <I>CDKAL1</I>, <I>CDKN2A</I>/<I>CDKN2B</I>, <I>IGF2BP2</I>, and <I>FTO</I> with risk for type 2 diabetes, with odds ratios ranging from 1.13 to 1.35 (1.3 × 10<SUP>−12</SUP> < <I>P</I><SUB>unadjusted</SUB> < 0.016). In addition, the A allele of rs8050136 at <I>FTO</I> was associated with increased BMI in the control subjects (<I>P</I><SUB>unadjusted</SUB> = 0.008). However, we did not observe significant association of any genetic variants with surrogate measures of insulin secretion or insulin sensitivity indexes in a subset of 2,662 control subjects. Compared with subjects carrying zero, one, or two risk alleles, each additional risk allele was associated with 17% increased risk, and there was an up to 3.3-fold increased risk for type 2 diabetes in those carrying eight or more risk alleles. Despite most of the effect sizes being similar between Asians and Europeans in the meta-analyses, the ethnic differences in risk allele frequencies in most of these genes lead to variable attributable risks in these two populations.</P><P><B>CONCLUSIONS—</B> Our findings support the important but differential contribution of these genetic variants to type 2 diabetes and obesity in Asians compared with Europeans.</P>

SLC12A3 (solute carrier family 12 member [sodium/chloride] 3) polymorphisms are associated with end-stage renal disease in diabetic nephropathy.

Kim, Jae Hyeon,Shin, Hyoung Doo,Park, Byung Lae,Moon, Min Kyong,Cho, Young Min,Hwang, Young Hwan,Oh, Kook Whan,Kim, Seong Yeon,Lee, Hong Kyu,Ahn, Curie,Park, Kyong Soo American Diabetes Association] 2006 Diabetes Vol.55 No.3

<P>Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD). Genetic susceptibility plays an important role in the development and progression of diabetic nephropathy. Previous studies have revealed that polymorphisms in the SLC12A3 (solute carrier family 12 member [sodium/chloride] 3) gene, which encodes solute carrier family 12 member 3, might contribute to genetic susceptibility to diabetic nephropathy and essential hypertension. In this study, we examined whether the SLC12A3 gene locus is associated with ESRD resulting from diabetic nephropathy. We genotyped 11 common single nucleotide polymorphisms (SNPs) in the SLC12A3 gene in 177 patients with ESRD due to type 2 diabetes and 184 patients with diabetic retinopathy but with no signs of renal involvement. Three SNPs (g.34372G>A [Arg913Gln], g.39143G>A, and g.41727C>T) were found to be associated with ESRD due to diabetic nephropathy. These three SNPs were in complete linkage disequilibrium. Haplotype 4 in block 2 (18806C, 21822C, 34372A, 39143A, 39240T, 39375C, and 41727T) showed a significant association with ESRD due to type 2 diabetes (P = 0.0028). These results suggest that the SLC12A3 gene locus is associated with ESRD due to diabetic nephropathy.</P>

Novel Promoter Polymorphism in RUNX2 Is Associated with Serum Triglyceride Level.

Shin, Hyoung Doo,Jeon, Jae-Pil,Park, Byung Lae,Bae, Joon Seol,Nam, Hye-Young,Shim, Sung-Mi,Park, Kyong Soo,Han, Bok-Ghee Korean Society for Molecular Biology 2008 Molecules and cells Vol.26 No.5

<P>Much research evidence supports the hypothesis that chronic, low-grade inflammation related to innate immunity may play an important role in the pathophysiology of type 2 diabetes mellitus (T2DM). Runt-related transcription factor 2 (RUNX2; MIM# 600211) acts as a scaffold that controls the integration, organization, and assembly of nucleic acids. To examine whether the novel promoter variant in RUNX2 is associated with the risk of T2DM and related phenotypes, RUNX2-742G > T was genotyped in 378 T2DM patients and 382 normal controls recruited in the Korean T2DM Study. Statistical analysis revealed that RUNX2-742G > T was associated with serum triglyceride level (TG) in nondiabetic controls, although it was not associated with the risk of T2DM. Individuals who carry T/T, T/G, and G/G genotypes had the highest (2.061 +/- 0.20), intermediate (2.01 +/- 0.19), and the lowest (1.97 +/- 0.18) levels of log [TG (mmol/l)] (P = 0.007), respectively. Our data on this important variant of RUNX2 suggest that lipid metabolism might be affected by genetic polymorphisms in the promoter region.</P>