Search for


TEXT SIZE

search for



CrossRef (0)
Association with Genetic Polymorphism of rs117033348 and Allergic Disease in Korean Population
Biomed Sci Letters 2021;27:177-181
Published online September 30, 2021;  https://doi.org/10.15616/BSL.2021.27.3.177
© 2021 The Korean Society For Biomedical Laboratory Sciences.

Yoonji Kong1,§,* , Mingyeong Kim1,§,* , Hyun-Seok Jin1,* * and Sangjung Park1,2,†,* *

1Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University, Asan, Chungnam 31499, Korea
2The Research Institute for Basic Sciences, Hoseo University, Asan, Chungnam 31499, Korea
Correspondence to: Sangjung Park. Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University, 20 Hoseo-ro 79 Beon-gil, Asan-si, Chungcheongnam-do 31499, Korea.
Tel: +82-41-540-9967, Fax: +82-41-540-9997, e-mail: sangjung@hoseo.edu
*Undergraduate student, **Professor.
§Yoonji Kong and Mingyeong Kim are equal contributors.
Received June 25, 2021; Revised September 14, 2021; Accepted September 16, 2021.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract
Allergy is an immune response that appears in certain people, and reactions such as coughing, shortness of breath, and hives occur. The immune system plays an important role in homeostasis and host defense, and allergies cause hypersensitivity reactions when an imbalance of immunity occurs. Mutations in the TLR genes are associated with autoimmune conditions such as allergies and asthma. It has been reported that a locus in the TLR1-TLR6-TLR10 region may be associated with atopic sensitization or allergy. Therefore, the purpose of this study was to select an allergy patient group and a healthy control group to determine how the genetic mutation of TLR1 affects the onset of disease. This study was conducted in 709 patients and 5,025 control groups out of 10,956 patients with data from KARE and HEXA cohorts. As a result of logistic regression analysis of 6 SNPs selected from the TLR1 gene, only rs117033348 showed a statistically significant correlation (P = 0.002356). The influence of rs117033348 was examined using PolyPhen-2, and a significant result was shown. Therefore, it can be predicted that the G base in rs117033348 will have an influence on the human body. In addition, Geography of Genetic Variants browser was used to confirm the geographical distribution of allele frequencies for the TLR1 gene. Although it was found that there was a large racial difference in the prevalence of TLR1 SNP, it could be confirmed that the polymorphism of rs117033348 conducted in this study was only specific in East Asia when compared with each race.
Keywords : Allergy, rs117033348, SNP, TLR1
Body

븣윭吏(allergy) 듅젙 궗엺뿉寃 굹굹뒗 硫댁뿭 諛섏쓳쑝濡 湲곗묠, 샇씉怨ㅻ, 몢뱶윭湲 벑쓽 諛섏쓳씠 씪뼱궃떎. 엫긽쟻쑝濡 씠윭븳 利앹긽씠 옱諛쒗븷 닔 엳쑝硫, 留뚯꽦솕 븯뒗 듅꽦쓣 媛뽯뒗떎(Jung et al., 1998). 硫댁뿭 泥닿퀎뒗 빆긽꽦怨 닕二 諛⑹뼱뿉 以묒슂븳 湲곕뒫쓣 븳떎. 뵲씪꽌 븣윭吏, 怨쇰쇱꽦 삉뒗 硫댁뿭怨 愿젴맂 硫댁뿭怨꾩쓽 遺덇퇏삎 븘넗뵾꽦 吏덊솚, 몢뱶윭湲, 삁愿遺醫낃낵 媛숈 吏덈퀝 諛 빟臾 怨쇰 諛섏쓳뿉꽌 留ㅼ슦 以묒슂븯湲 븣臾몄뿉 솚옄쓽 궣쓽 吏덉뿉 쁺뼢쓣 誘몄튌 닔 엳쑝硫, 吏냽쟻씤 愿由ъ 移섎즺媛 븘슂빐 쟾 꽭怨꾩쟻쑝濡 궗쉶寃쎌젣쟻 遺떞씠 利앷븯怨 엳떎(Simon, 2019; Choi and Kong, 2021). 븣윭吏 吏덊솚쓽 諛쒖깮瑜좉낵 쑀蹂묐쪧 쟾 꽭怨꾩쟻쑝濡 袁몄엳 利앷븯怨 엳쑝硫, 10뀈씠 吏궇닔濡 듅엳 뼱由곗씠 泥뀈痢듭뿉꽌 利앷븯怨 엳뒗 寃껋쑝濡 븣젮졇 엳떎. 븯吏留 씠윭븳 利앷뿉룄 븣윭吏 諛쒕퀝뿉 븳 쓽猷 湲곗닠 媛쒖꽑릺吏 븡怨 엳떎(Diwakar et al., 2017). 꽌援 깮솢 諛⑹떇怨 삤옯룞븞 뿰愿릺뼱 솕뜕 븣윭吏 吏덊솚 븘떆븘 씤룄뿉꽌 쑀蹂묐쪧씠 넂븘吏怨 엳쑝硫, 븳援 뿭떆 吏궃 20뀈 룞븞 늿뿉 쓣寃 利앷븯떎(Simon, 2019; Park et al., 2009). 븣윭吏 吏덊솚 쁺쑀븘뿉꽌 쐞옣愿, 泥냼뀈 샇씉湲, 꽦씤뿉꽌뒗 떖삁愿怨 삁븬 利앹긽씠 굹궃떎. 씠泥섎읆 굹씠뿉 뵲씪 利앹긽쓽 뼇긽씠 蹂솕븯뒗 寃곌낵媛 蹂닿퀬릺뿀떎(Goh et al., 2018). 삉븳 븣윭吏 諛섏쓳씠 떖븷 寃쎌슦 븘굹븘씫떆뒪媛 諛쒖깮븷 닔 엳怨, 諛쒕퀝씠 鍮좊Ⅴ硫 냼웾쓽 빆썝뿉 쓽빐 쑀諛쒕맆 닔 엳뼱 깮紐낆쓣 쐞삊븯뒗 샇씉 諛 닚솚 臾몄젣瑜 듅吏뺤쑝濡 븯뒗 以묒쬆쓽 쟾떊꽦 怨쇰 諛섏쓳쑝濡 굹궇 닔 엳떎(Reber et al., 2017). 븣윭吏뒗 쑀쟾 媛뒫꽦씠 넂븘 븣윭吏 吏덊솚쓽 쑀쟾쟻 湲곗큹瑜 諛앺엳湲 쐞븳 留롮 끂젰씠 엳뿀떎(Bønnelykke et al., 2015; Potaczek et al., 2017). 븯吏留 吏덈퀝뿉 븳 吏떇怨 뜑 굹 씠빐媛 슂援щ릺硫, 븣윭吏 吏덊솚쓽 理쒖쟻솕맂 삁諛⑹씠 븘슂븯떎(Charfi et al., 2010).

Toll-like-receptor (TLR) 移⑥엯븯뒗 蹂묒썝泥대 씤떇븯怨 꽑泥 硫댁뿭쓣 솢꽦솕븯뒗뜲 以묒슂븳 뿭븷쓣 븯뒗 留 愿넻 닔슜泥댁씠떎(Gao et al., 2016). 븣윭吏 吏덊솚쓽 諛쒕퀝 湲곗쟾뿉꽌 TLR 닔슜泥댁쓽 뿭븷 硫댁뿭 諛섏쓳쓽 솢꽦솕 諛 議곗젅뿉 옉슜븯뒗 깮臾쇳븰쟻 湲곕뒫뿉 湲곗씤븳떎(Dębińska and Boznański, 2014). 硫댁뿭怨 꽭룷뒗 듅젙 蹂묒썝泥 愿젴 遺꾩옄 뙣꽩(Pathogen Associated Molecular Pattern, PAMP)쓣 씤떇븯뿬 쐞뿕쓣 媛먯븯怨, 듅젙 硫댁뿭 諛섏쓳쓣 씪쑝궎뒗 떎뼇븳 뙣꽩 씤떇 닔슜泥(Pattern Recognition Receptor, PRR)瑜 諛쒗쁽븳떎. TLR 삉븳 떎뼇븳 硫댁뿭 꽭룷뿉 쓽빐 諛쒗쁽릺뒗 PRR 以 븯굹씠떎(Vijay, 2018). 吏吏 떎떦瑜(LPS), 吏떒諛깆쭏, 렪紐 諛 諛뺥뀒由ъ븘 DNA瑜 룷븿븳 愿묐쾾쐞븳 誘몄깮臾 궛臾쇱쓽 씤떇쓣 留ㅺ컻븯怨, TLR쓣 넻븳 떊샇 쟾떖 뿼利 留ㅺ컻泥댁쓽 깮꽦쑝濡 씠뼱吏꾨떎(Jang et al., 2017). 誘몄깮臾쇱뿉 쓽븳 TLR 옄洹뱀 빆썝젣떆꽭룷瑜 솢꽦솕븯硫, 議곗젅 T 꽭룷(Treg) 湲곕뒫뿉 쁺뼢쓣 誘몄퀜 Th1/Th2 洹좏삎 諛 Th17 꽭룷 遺꾪솕瑜 寃곗젙븯怨, 鍮꾨쭔 꽭룷뿉꽌 궗씠넗移댁씤 깮궛 諛 샇궛援 솢꽦솕瑜 젣뼱븳떎(Dębińska and Boznański, 2014). 븯吏留 TLR 떊샇 쟾떖 寃쎈줈쓽 議곗젅 옣븷뒗 븣윭吏 諛 泥쒖떇, 留뚯꽦 鍮꾨鍮꾨룞뿼, 뿼利앹꽦 옣 吏덊솚, 二쎌긽 룞留 寃쏀솕利앷낵 媛숈씠 뿬윭 옄媛 硫댁뿭 삉뒗 뿼利앹꽦 吏덊솚쓽 蹂묒씤뿉 愿뿬븳떎怨 븣젮졇 엳떎(Patra et al., 2020). 삉븳 寃뚮냸 쟾泥 뿰援ъ쓽 硫뷀 遺꾩꽍(Genome Wide Meta Analysis)뿉 쓽븯硫 TLR1-TLR6-TLR10 쁺뿭쓽 쑀쟾옄醫뚮뒗 븘넗뵾 媛먯옉 삉뒗 븣윭吏 뿰愿맆 닔 엳떎怨 蹂닿퀬릺뿀떎(Renkonen et al., 2015). 뵲씪꽌 TLR 쑀쟾옄쓽 蹂씠뒗 븣윭吏 諛 泥쒖떇怨 媛숈 옄媛硫댁뿭 吏덊솚怨 愿젴씠 엳쓬쓣 蹂댁뿬以떎(Koponen et al., 2014). 蹂 뿰援щ뒗 븳援씤 쑀쟾泥 뿭븰 議곗궗 궗뾽 肄뷀샇듃 옄猷뚮 솢슜븯뿬 븣윭吏 솚옄援곌낵 嫄닿컯 議곌뎔쓣 꽑蹂꾪빐 TLR1쓽 쑀쟾쟻 蹂씠媛 吏덈퀝 諛쒕퀝뿉 뼱뼚븳 쁺뼢쓣 二쇰뒗吏 솗씤븯怨좎옄 븯떎.

뿰援 긽옄뒗 븳援씤 쑀쟾泥 뿭븰 議곗궗 궗뾽(Korean Genome and Epidemiology Study; KoGES)쓽 씪솚씤 KARE (Korean Association Resource) HEXA (The Health Examinees) 肄뷀샇듃 옄猷뚮 遺꾩뼇諛쏆븘 솢슜븯떎(KBN-2017-046) (Cho et al., 2009; Health Examinees Study Group, 2015). 40꽭 씠긽쓽 궓瑜 룷븿븳 珥 10,956紐(KARE: 7,524紐, HEXA: 3,432紐) 以 븣윭吏 吏덊솚쑝濡 吏꾨떒諛쏆 709紐낆쓣 솚옄援곗쑝濡 꽑蹂꾪븯떎. 洹몃━怨 泥쒖떇, 怨좏삁븬, 떦눊, 떖洹쇨꼍깋, 뇤議몄쨷, 媛묒긽꽑 吏덊솚, 怨좎삁利, 留뚯꽦룓뇙꽦 룓 吏덊솚怨 넻뭾뿉 븳 怨쇨굅젰씠 뾾뒗 5,014紐낆쓣 嫄닿컯 議곌뎔쑝濡 꽑蹂꾪븯떎. 븣윭吏 솚옄援곌낵 嫄닿컯 議곌뎔쓽 엫긽쟻 듅꽦쓣 Table 1뿉 굹깉떎. 씠踰 뿰援ъ뿉 솢슜븳 쑀쟾젙蹂대뒗 吏덈퀝愿由ъ껌(KDCA)怨 샇꽌븰援먯뿉꽌 뿰援 쑄由 듅씤(104131-170822-BR-062-01)쓣 諛쏆븘 닔뻾븯떎. 珥 10,956紐낆쓽 쑀쟾삎 遺꾩꽍 Exome 쁺뿭쓽 遺꾩꽍쓣 쐞빐 Illumina HumanExome Chip v1.1 (Illumina, Inc., San Diego, CA, USA) exome chip쓣 궗슜븯뿬 遺꾩꽍릺뿀떎. 뭹吏 愿由(QC) 怨쇱젙뿉꽌 DNA 떆猷뚮뒗 뿰援 李몄뿬옄쓽 留먯큹 삁븸뿉꽌 遺꾨━ 異붿텧븯怨, 쑀쟾삎 뙋룆 젙솗룄媛 96% 씠븯씠嫄곕굹, 怨쇰룄븳 heterozygosity瑜 媛吏嫄곕굹, 꽦蹂 遺덉씪移섍 議댁옱븯뒗 긽옄뱾 젣쇅릺뿀떎. 蹂 뿰援ъ뿉꽌뒗 珥 77,311媛쒖쓽 SNP쓣 긽쑝濡 marker QC瑜 닔뻾븯뿬 MAF媛 1% 誘몃쭔씤 SNP怨 쟾泥 遺꾩꽍 긽옄 以 1% 씠긽쓽 寃곌낵媛 늻씫맂 SNP쓣 젣쇅븳 썑 珥 31,506媛쒖쓽 SNP쓣 遺꾩꽍뿉 궗슜븯떎(Marees et al., 2018). 뿼깋泥 긽쓽 쐞移섎뒗 UCSC (University of Colombo school of computing) Genome browser on human Feb, 2009 (Genome Reference Consortium Human Build 37)瑜 湲곗쑝濡 븯떎. 遺遺꾩쓽 넻怨 遺꾩꽍뿉뒗 PLINK version 1.90 beta (http://pngu.mgh.harvard.edu/~purcell/plink) PASW Statistics version 21.0 (SPSS Inc. Chicago, IL, USA)쓣 궗슜븯떎. 븣윭吏 솚옄援곌낵 嫄닿컯 議곌뎔뿉 븳 쑀쟾 蹂씠쓽 긽愿 遺꾩꽍 濡쒖뒪떛 쉶洹 遺꾩꽍쓣 궗슜븯뿬 GWAS瑜 떆뻾븯떎. 쉶洹 遺꾩꽍쓽 떆뻾뿉 엳뼱꽌 굹씠 꽦蹂꾩쓣 怨듬닔濡 議곗젙븯뿬 遺꾩꽍븯怨, 遺꾩꽍 媛믪뿉 븳 쑀쓽꽦쓽 湲곗 0.05 誘몃쭔쓣 湲곗쑝濡 븯떎.

Basic characteristics of the subjects in the Exome Chip

Characteristics Controls Cases P-value
Number of subjects 5,014 709 -
Gender [men (%) / women (%)] 2562 (51.1) / 2452 (48.9) 245 (34.6) / 464 (65.4) <0.05
Age (M years ± SD) 50.81±8.55 51.25±8.09 <0.05

Abbreviations: Exome Chip; M, mean value; SD, standard deviation



GWAS 遺꾩꽍 寃곌낵, 븣윭吏 吏덊솚怨 bonferroni correction (6.46×10-7)쓽 寃곌낵瑜 蹂댁씤 SNP뒗 議댁옱븯吏 븡븯떎. 뵲씪꽌 빐떦 寃곌낵瑜 媛 쑀쟾옄 젅踰⑤줈 媛쒕퀎 遺꾩꽍쓣 닔뻾븯怨 븣윭吏 뿰愿맂 1,621媛쒖쓽 SNP쓣 솗씤븯떎. 洹 以 긽쟻 쐞뿕룄(Odds ratio, OR)媛 1.3 씠긽씠硫댁꽌 P-value 媛 10-3 씠븯뿉 냽븯뒗 230媛쒖쓽 SNP쓣 궛異쒗븯怨, 븣윭吏 諛쒕퀝뿉 넂 媛먯닔꽦쓣 蹂댁씠硫 GGV 寃곌낵瑜 넻빐 룞븘떆븘뿉꽌 듅씠쟻쑝濡 諛쒗쁽븯뒗 SNP쓣 媛吏 TLR1 쑀쟾옄瑜 꽑젙븯떎. 씠瑜 諛뷀깢쑝濡 TLR1 쑀쟾옄瑜 긽쑝濡 濡쒖뒪떛 쉶洹 遺꾩꽍쓣 떆뻾븯떎. 洹 寃곌낵 븯굹쓽 SNP씠 룄異쒕릺뿀怨, 넻怨꾩쟻쑝濡 쑀쓽븳 긽愿愿怨꾩엫쓣 솗씤븷 닔 엳뿀떎(Table 2). Additive Model뿉꽌쓽 OR 媛믪 1.385, 떊猶곌뎄媛(95% CI) 1.122~1.708씠硫, Dominant Model뿉꽌쓽 OR 媛믪 1.398, 떊猶곌뎄媛꾩 1.121~1.744씠떎. 삉븳 Minor Allele Frequency (MAF)뒗 嫄닿컯 議곌뎔뿉꽌 6.2%쓽 鍮덈룄瑜 굹궡硫, 븣윭吏 솚옄援곗뿉꽌뒗 8.2%濡 2%쓽 鍮덈룄 李④ 엳떎. 뵲씪꽌 Minor allele씤 G 뿼湲곕 蹂댁쑀븷 寃쎌슦 븣윭吏 諛쒕퀝쓣 利앷떆궎뒗 諛⑺뼢쑝濡 긽愿꽦씠 엳떎뒗 寃껋쓣 솗씤븷 닔 엳뿀떎.

Result of the case-control association analysis between SNP in the TLR1 genes and allergy in the Exome Chip subjects

GENE CHR SNP Minor allele BP MAF (n) Genetic Model OR (95% CI) P-value
Controls Cases
TLR1 4p14 rs117033348 G 38800022 0.062 (617) 0.082 (116) ADD 1.385 (1.122~1.708) 2.38×10-3
DOM 1.398 (1.121~1.744) 2.92×10-3

P-value < 0.05 is indicated in bold; CHR, chromosome; SNP, single nucleotide polymorphism; BP, base pair; MAF, minor allele frequency; n, number of minor; OR, odds ratio; CI, confidence interval. The SNP position are based on the UCSC build 37



PolyPhen-2瑜 솢슜븯뿬 븣윭吏뿉꽌 넻怨꾩쟻씤 쑀쓽꽦쓣 蹂댁씤 rs117033348씠 媛吏뒗 쁺뼢젰쓣 븣븘蹂댁븯떎(Fig. 1). PolyPhen-2뒗 븘誘몃끂궛쓽 移섑솚씠 떒諛깆쭏쓽 援ъ“ 湲곕뒫쓽 李⑥씠濡 씤빐 씤媛꾩뿉寃 誘몄튂뒗 쁺뼢젰쓣 Probably Damaging Score濡 삁痢≫븷 닔 엳떎. Score뒗 0뿉꽌 1源뚯 BENIGN, PROBABLY DAMAGING, POSSIBLY DAMAGING 珥 3媛吏濡 몴쁽릺硫, 1뿉 媛源뚯썙吏덉닔濡 겙 쁺뼢쓣 誘몄튌 寃껋쑝濡 삁긽븷 닔 엳떎. rs117033348쓽 寃곌낵뒗 븘誘몃끂궛쓽 蹂솕濡 씤빐 겙 쁺뼢쓣 以 닔 엳뒗 1濡 굹궗떎. 삉븳 꽭怨꾩쟻쑝濡 遺꾪룷븯怨 엳뒗 媛 씤醫낆쓽 rs117033348쓽 G 뿼湲 鍮덈룄瑜 Geography of Genetic Variants (GGV) browser쓣 씠슜븯뿬 븣븘蹂댁븯떎(Fig. 2). GGV뒗 1000 genome project쓽 뜲씠꽣踰좎씠뒪瑜 湲곕컲쑝濡 듅젙 씤醫낅뱾쓽 뿼湲 鍮덈룄瑜 蹂댁뿬以떎. 씠쟾 뿰援ъ뿉꽌 TLR1 SNP쓽 쑀蹂묐쪧 씤醫낆쟻쑝濡 겙 李⑥씠媛 엳떎怨 蹂닿퀬릺뿀떎(Yang and Chiang, 2017). 蹂 뿰援ъ뿉꽌 吏꾪뻾븳 rs117033348쓽 떎삎꽦 뿭떆 媛곴컖쓽 씤醫낃낵 鍮꾧탳븯쓣 븣 룞븘떆븘 吏뿭뿉꽌留 듅씠쟻쑝濡 굹굹怨 엳쓬쓣 솗씤븷 닔 엳뿀떎.

Fig. 1. Confirmation of the probably damaging score of rs117033348 of the TLR1 gene using PolyPhen-2. The rs117033348 showing the highest score for predicted score is marked by black line. This report is HumDiv. The HumDiv model is preferres model for evaluating rare alleles, dense mapping of regions identifies by genome-wide association studies, ans analysis of natural selection. http://genetics.bwh.harvard.edu/cgi-bin/pph2/dbsearch.cgi?dbid=77810520

Fig. 2. Confirmation of rs117033348 minor allele frequency of TLR1 through Geography of Genetic Variants browser (GGV). The 1000 Genomes project consortium data is used to represent the allele frequencies of ethnic group. G allele is marked in green and is rarely found in other groups but concentrated in East Asia. MAF of CHB (Han Chinese in Beijing, China), CHS (Han Chinese South, China), and KHV (Kinh in Ho Chi Minh City, Vietnam) populations were less than 0.01. The red arrow indicates the JPT (Japanese in Tokyo, Japan) population, and the MAF is 0.038 which indicated in green inside the circle.

TLR1 꽭洹좎꽦 吏吏 떒諛깆쭏 諛 吏吏 렔떚뱶瑜 씤떇븯湲 쐞빐 TLR2 씠醫낆씠웾泥대 삎꽦븯뒗 寃껋쑝濡 븣젮졇 엳떎(Jin et al., 2007). TLR2-TLR1 씠醫낆씠웾泥대뒗 洹몃엺쓬꽦 꽭洹 諛 誘몄퐫뵆씪뒪留덉뿉꽌 Triacylated Lipopeptides瑜 씤떇븳떎(Kawai and Akira, 2010). 삉븳 Pam3CSK4뒗 TLR1뿉 쓽빐 留ㅺ컻릺뒗 빀꽦 TLR 由ш컙뱶濡, 꽭룷吏 룄硫붿씤쓣 넻빐 TLR2 삊젰븯뿬 떊샇 쟾떖 Cascade瑜 쑀룄빐 NF-κB 떊샇 쟾떖 寃쎈줈瑜 솢꽦솕븳떎(West et al., 2011). NF-κB쓽 솢꽦솕뒗 뿼利 怨쇱젙쓽 떆옉뿉 愿뿬븯뒗 궗씠넗移댁씤怨 耳紐⑥뭅씤쓣 븫샇솕븯뒗 쑀쟾옄쓽 쟾궗瑜 쑀룄븳떎(Kwok et al., 2012). 븯吏留 TLR1쓽 쑀쟾쟻 蹂씠뒗 씠윭븳 NF-κB 寃쎈줈쓽 솢꽦솕瑜 겕寃 媛먯냼떆궎硫, 硫댁뿭 諛섏쓳뿉 빐濡쒖슫 쁺뼢쓣 誘몄튌 媛뒫꽦씠 넂븘 뿼利앹뿉 븳 媛먯닔꽦뿉 湲곗뿬븷 닔 엳쓬쓣 떆궗븳떎(Ben-Ali et al., 2011).

뵲씪꽌 씠踰 뿰援щ뒗 TLR1 쑀쟾옄쓽 SNP뿉꽌 룞븘떆븘씤씠 Minor allele씤 G 뿼湲곕 媛議뚯쓣 寃쎌슦 븣윭吏뿉 븳 媛먯닔꽦씠 利앷븯怨 엳쓬쓣 蹂댁뿬二쇱뿀떎. 떎留 蹂 뿰援ъ뿉꽌뒗 Exomchip쓣 씠슜븳 遺꾩꽍 寃곌낵瑜 솢슜븯뿬 marker QC뿉꽌 MAF媛 留ㅼ슦 궙 marker뱾씠 젣쇅릺뼱 떎젣 TLR1 쑀쟾옄뿉꽌뒗 1媛쒖쓽 SNP留뚯쓣 솗씤븷 닔 엳뿀떎. 異뷀썑 떎瑜 肄뷀샇듃뿉꽌 룞씪븳 쑀쟾泥 쁺뿭뿉 븳 異붽 뿰援ш 븘슂븷 寃껋쑝濡 蹂댁씤떎. 吏궃 닔떗 뀈 룞븞 泥쒖떇, 뵾遺뿼 諛 鍮꾩뿼怨 媛숈 븣윭吏 븘넗뵾 옣븷쓽 利앷媛 愿李곕릺뿀吏留 씠윭븳 湲곗쟾 븘吏 紐낇솗븯吏 븡븘 깉濡쒖슫 移섎즺踰뺤쓽 媛쒕컻씠 젣븳쟻씠떎(Verschoor and von Gunten, 2019). 븯吏留 쁽옱源뚯 븣윭吏쓽 諛쒖깮怨 솚寃 諛 쑀쟾쟻 슂씤怨쇱쓽 긽愿愿怨꾩뿉 븳 뿰援щ뱾씠 留롮씠 吏꾪뻾릺怨 엳쑝硫, 蹂 뿰援щ뒗 TLR1쓽 쑀쟾쟻 떎삎꽦씠 븣윭吏 諛쒕퀝뿉 쁺뼢쓣 誘몄튌 닔 엳쓬쓣 젣떆븯怨 엳떎. 씠寃껋 삉븳 븣윭吏 諛쒕퀝쓽 씠빐뿉 룄쓣 以 닔 엳쓣 寃껋쑝濡 湲곕맂떎.

ACKNOWLEDGEMENT

Following are results of a study on the "Leaders in INdustry-university Cooperation +" Project, supported by the Ministry of Education and National Research Foundation of Korea

CONFLICT OF INTEREST

The authors have no conflicts of interest to disclose.

References
  1. Ben-Ali M, Corre B, Manry JManry J et al. Functional characterization of naturally occurring genetic variants in the human TLR1-2-6 gene family. Hum Mutat. 2011. 32: 643-652.
    Pubmed CrossRef
  2. B첩nnelykke K, Sparks R, Waage J, Milner JD. Genetics of allergy and allergic sensitization: common variants, rare mutations. Curr Opin Immunol. 2015. 36: 115-126.
    Pubmed KoreaMed CrossRef
  3. Charfi A, Zainine R, Ben Ali SBen Ali S et al. Rhinites allergiques [Allergic rhinitis]. Tunis Med. 2010. 88: 690-695.
  4. Cho YS, Go MJ, Kim YJKim YJ et al. A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat Genet. 2009. 41: 527-534.
    Pubmed CrossRef
  5. Choi HG, Kong IG. Asthma, Allergic Rhinitis, and Atopic Dermatitis Incidence in Korean Adolescents before and after COVID-19. J Clin Med. 2021. 10: 3446.
    Pubmed KoreaMed CrossRef
  6. D휌bi흦ska A, Bozna흦ski A. The role of Toll-like receptors in the pathogenesis of allergic diseases - where is the truth? Postepy Hig Med Dosw (Online). 2014. 7; 68: 230-237.
    Pubmed CrossRef
  7. Diwakar L, Cummins C, Lilford R, Roberts T. Systematic review of pathways for the delivery of allergy services. BMJ Open. 2017. 7: e012647.
    Pubmed KoreaMed CrossRef
  8. Gao J, Wei L, Wei JWei J et al. TLR1 polymorphism rs4833095 as a risk factor for IgA nephropathy in a Chinese Han population: A case-control study. Oncotarget. 2016. 7: 83031-83039.
    Pubmed KoreaMed CrossRef
  9. Goh SH, Soh JY, Loh WLoh W et al. Cause and Clinical Presentation of Anaphylaxis in Singapore: From Infancy to Old Age. Int Arch Allergy Immunol. 2018. 175: 91-98.
    Pubmed CrossRef
  10. Health Examinees Study Group. The Health Examinees (HEXA) study: rationale, study design and baseline characteristics. Asian Pac J Cancer Prev. 2015. 16: 1591-1597.
    Pubmed CrossRef
  11. Jang YH, Choi JK, Jin MJin M et al. House Dust Mite Increases pro-Th2 Cytokines IL-25 and IL-33 via the Activation of TLR1/6 Signaling. J Invest Dermatol. 2017. 137: 2354-2361.
    Pubmed CrossRef
  12. Jin MS, Kim SE, Heo JYHeo JY et al. Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell. 2007. 130: 1071-1082.
    Pubmed CrossRef
  13. Jung AN, Lee SR, Kim SY, Kang HJ, Lee KH, Cho YS. Analysis of MAST test result for 1 year. Korean J Clin Lab Sci. 1998. 30: 162-168.
  14. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010. 11: 373-384.
    Pubmed CrossRef
  15. Koponen P, Vuononvirta J, Nuolivirta K, Helminen M, He Q, Korppi M. The association of genetic variants in toll-like receptor 2 subfamily with allergy and asthma after hospitalization for bronchiolitis in infancy. Pediatr Infect Dis J. 2014. 33: 463-466.
    Pubmed CrossRef
  16. Kwok YH, Hutchinson MR, Gentgall MG, Rolan PE. Increased responsiveness of peripheral blood mononuclear cells to in vitro TLR 2, 4 and 7 ligand stimulation in chronic pain patients. PLoS One. 2012. 7: e44232.
    Pubmed KoreaMed CrossRef
  17. Marees AT, de Kluiver H, Stringer SStringer S et al. A tutorial on conducting genome-wide association studies: Quality control and statistical analysis. Int J Methods Psychiatr Res. 2018. 27: e1608.
    Pubmed KoreaMed CrossRef
  18. Patra MC, Achek A, Kim GYKim GY et al. A Novel Small-Molecule Inhibitor of Endosomal TLRs Reduces Inflammation and Alleviates Autoimmune Disease Symptoms in Murine Models. Cells. 2020. 9: 1648.
    Pubmed KoreaMed CrossRef
  19. Park HS, Choi GS, Cho JS, Kim YY. Epidemiology and current status of allergic rhinitis, asthma, and associated allergic diseases in Korea: ARIA Asia-Pacific workshop report. Asian Pac J Allergy Immunol. 2009. 27: 167-171.
    Pubmed
  20. Potaczek DP, Harb H, Michel SMichel S et al. Epigenetics and allergy: from basic mechanisms to clinical applications. Epigenomics. 2017. 9: 539-571.
    Pubmed CrossRef
  21. Reber LL, Hernandez JD, Galli SJ. The pathophysiology of anaphylaxis. J Allergy Clin Immunol. 2017. 140: 335-348.
    Pubmed KoreaMed CrossRef
  22. Renkonen J, Toppila-Salmi S, Joenv채채r채 SJoenv채채r채 S et al. Expression of Toll-like receptors in nasal epithelium in allergic rhinitis. APMIS. 2015. 123: 716-725.
    Pubmed KoreaMed CrossRef
  23. Simon D. Recent Advances in Clinical Allergy and Immunology 2019. Int Arch Allergy Immunol. 2019. 180: 291-305.
    Pubmed CrossRef
  24. Verschoor D, von Gunten S. Allergy and Atopic Diseases: An Update on Experimental Evidence. Int Arch Allergy Immunol. 2019. 180: 235-243.
    Pubmed CrossRef
  25. Vijay K. Toll-like receptors in immunity and inflammatory diseases: Past, present, and future. Int Immunopharmacol. 2018. 59: 391-412.
    Pubmed KoreaMed CrossRef
  26. West AP, Brodsky IE, Rahner CRahner C et al. TLR signalling augments macrophage bactericidal activity through mitochondrial ROS. Nature. 2011. 472: 476-480.
    Pubmed KoreaMed CrossRef
  27. Yang CA, Chiang BL. Toll-like receptor 1 N248S polymorphism affects T helper 1 cytokine production and is associated with serum immunoglobulin E levels in Taiwanese allergic patients. J Microbiol Immunol Infect. 2017. 50: 112-117.
    Pubmed CrossRef