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Replication Association Study between RBC Indices and Genetic Variants in Korean Population
Biomed Sci Letters 2019;25:190-195
Published online June 30, 2019;  https://doi.org/10.15616/BSL.2019.25.2.190
© 2019 The Korean Society For Biomedical Laboratory Sciences.

Sang In Lee*, Sangjung Park,** and Hyun-Seok Jin,**

Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University, Asan, Chungnam 31499, Korea
Correspondence to: These authors are equally contributed.
Sangjung Park. Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University, Asan, Chungnam 31499, Korea.
Tel: +82-41-540-9967, Fax: +82-41-540-9997, e-mail: sangjung@hoseo.edu
Hyun-Seok Jin. Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University, Asan, Chungnam 31499, Korea.
Tel: +82-41-540-9968, Fax: +82-41-540-9997, e-mail: jinhs@hoseo.edu
Received June 14, 2019; Revised July 1, 2019; Accepted July 2, 2019.
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

Hemoglobin (Hb) concentrations and hematocrit (Hct) values can be changed by factors such as erythrocyte production, destruction, and bleeding. In addition, variants in the protein expression involved in the amount of red blood cells that determine Hb metabolism or Hct value can increase susceptibility to complex blood diseases. Previous studies have reported significant single nucleotide polymorphisms (SNPs) by applying a genome-wide association study (GWAS) on Hb levels and Hct values in European population. In this study, we confirmed whether the significant SNPs are replicated in Koreans. In previous studies, 26 and 18 SNPs with a significant correlation Hb and Hct were identified in Korean genotype data, and 21 and 12 SNPs were selected, respectively. The SNPs of PRKCE (rs10495928), TMPRSS6 (rs2235321, rs5756505, rs855791) were significantly associated with Hb (P<0.05). In the association analysis of Hct, the SNPs of HBS1L (rs6920211, rs9389268, rs9483788), PRKCE (rs4953318), SCGN (rs9348689) and TMPRSS6 (rs2413450) genes showed a significant correlation (P<0.05). Replicated SNPs and not replicated SNPs showed the difference of genetic distance calculated by Fst. The replicated SNPs with a significant correlation showed similar allele frequencies, whereas the not replicated SNPs showed a large difference in allele frequency. All replicated SNPs with significant correlations had Fst values less than 0.05, indicating that the genetic distance between the groups was close. On the other hand, the not replicated SNPs showed that the Fst value was 0.05 or more and the genetic distance was relatively large.

Keywords : Genetic association, Hematocrit, Hemoglobin, Single nucleotide polymorphism
Body
emoglobin (Hb) 쟻삁援ъ뿉 議댁옱븯뒗 궛냼슫諛 떒諛깆쭏씠硫, Hematocrit (Hct) 삁븸뿉꽌 쟻삁援ш 李⑥븯怨 엳뒗 슜쟻쓽 鍮꾩쨷쓣 諛깅텇쑉濡 몴떆븳 寃껋씠떎. 삁援 議고삁뿉 臾몄젣媛 깮湲곌굅굹 쟻삁援 뙆愿댁 媛숈 吏덊솚씠 諛쒖깮븯硫 Hb 냽룄 Hct 媛믪씠 鍮꾩젙긽쟻 닔移섎 굹궡寃 맂떎. Hb 뿴 援ъ“뿉 2媛 泥 씠삩쓣 媛吏怨 엳쓣 븣 궛냼슫諛 湲곕뒫쓣 븯寃 릺뒗뜲, 씠윭븳 怨쇱젙뿉 愿뿬븯뒗 떒諛깆쭏 諛쒗쁽뿉 씠긽씠 깮湲 寃쎌슦뿉 湲곕뒫쟻 Hb쓽 닔媛 以꾩뼱뱾寃 릺뼱 鍮덊삁쓣 쑀諛쒗븷 닔 엳떎. 씠윭븳 吏덊솚씪 諛쒖깮븯寃 릺硫 吏덈퀝쓽 蹂댁긽쟻 옉슜쑝濡 湲곕뒫쟻 Hb쓽 蹂댁땐쓣 쐞븳 議고삁옉슜씠 씠猷⑥뼱吏怨 Hb 냽룄 Hct 媛믪씠 젙긽蹂대떎 긽듅븯寃 맂떎. Hb怨 Hct 닔移섏쓽 긽듅 삁븸쓽 젏룄瑜 利앷떆耳 삁愿吏덊솚쓣 쑀諛쒗븷 닔 엳떎. 뵲씪꽌 Hb 냽룄 Hct 媛믨낵 愿젴맂 떒諛깆쭏쓽 蹂솕뒗 삁븸愿젴 蹂듯빀吏덊솚뿉 븳 媛먯닔꽦쓣 利앷떆궗 닔 엳떎怨 븣젮졇 엳떎(Amr et al., 2019; Grimholt et al., 2019; Paradowska-Gorycka et al., 2019).

Zhong et al. 쑀읇씤쓣 긽쑝濡 Hb怨 Hct뿉 븳 쟾옣 쑀쟾泥 遺꾩꽍뿰援(Genome-wide association study, GWAS)瑜 떆뻾븯뿬 쑀쓽꽦 엳뒗 SNP (Single Nucleotide Polymorphisms)뱾쓣 諛쒗몴븯떎(Zhong et al., 2016). Hb 냽룄쓽 긽愿 遺꾩꽍뿉꽌 HFE 쑀쟾옄쓽 rs1800562 (P=1.06×10-15), HIST1H1C 쑀쟾옄쓽 rs9295685 (P=4.11×10-13) 룷븿 珥 18 쑀쟾옄 궡 26 SNP뿉꽌 넻怨꾩쟻 쑀쓽꽦씠 솗씤릺뿀떎. Hct 媛믨낵쓽 긽愿 遺꾩꽍뿉꽌뒗 PRKCE 쑀쟾옄쓽 rs4953318 (P= 1.18×10-12), HBS1L 쑀쟾옄쓽 rs9483788 (P=3.55×10-11) 룷븿븯뿬 珥 14媛 쑀쟾옄 쁺뿭 궡 18媛쒖쓽 SNP뿉꽌 넻怨꾩쟻 쑀쓽꽦씠 솗씤릺뿀떎. 뵲씪꽌 蹂 뿰援ъ뿉꽌뒗 쑀읇씤 肄뷀샇듃瑜 긽쑝濡 Hb, Hct 뿰愿릺뼱 엳뒗 쑀쟾옄 쑀쟾쟻 떎삎꽦쓽 쑀쓽븳 긽愿 愿怨꾧 븳援씤 긽쓽 쑀쟾泥 뿭븰 肄뷀샇듃瑜 湲곕컲쑝濡 遺꾩꽍븯쓣 븣뿉룄 옱쁽꽦씠 엳뒗吏瑜 솗씤븯怨좎옄 븯떎.

꽑뻾맂 뿰援ъ뿉꽌 Hb, Hct뿉 빐 쟾옣 쑀쟾泥 遺꾩꽍 Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium(쑀읇씤 怨꾪넻 24,167紐)怨 HaemGen Consortium(쑀읇씤 怨꾪넻 9,456紐)쓣 湲곕컲쑝濡 븯떎(Ganesh et al., 2009; Soranzo et al., 2009). Hb 닔移섏쓽 긽愿 遺꾩꽍뿉꽌 넂 쑀쓽닔以(P≤5×10-8)쓣 留뚯”븯뒗 SNP 씠 26媛쒖怨, Hct뿉꽌뒗 18媛쒖쓽 SNP뱾씠 GWAS 쑀쓽닔以쓣 留뚯”븯怨 엳뿀떎(Zhong et al., 2016). 긽愿 遺꾩꽍 떆 Hb 냽룄 Hct 媛믪쓣 긽듅븯뒗 諛⑺뼢쑝濡 쁺뼢쓣 二쇰뒗 allele瑜 effect allele濡 吏젙븯떎.

蹂 뿰援щ 쐞븳 븳援씤 뿰援щ긽옄뒗 븳援씤 쑀쟾泥 뿭븰 議곗궗 궗뾽(Korean Genome and Epidemiology Study; KoGES)쓽 씪솚씤 Korean Association Resource (KARE)瑜 긽쑝濡 븯떎(Cho et al., 2009). 씠븣 씠슜븳 옄猷뚮뒗 吏덈퀝愿由щ낯遺 씤泥댁옄썝뻾뿉꽌 遺꾩뼇쓣 諛쏆븘 궗슜븯떎. 珥 궓 10,038紐 以 QC (Quality Control) 怨쇱젙쓣 넻怨쇳븳 8,840紐낆쓣 꽑젙븯떎(Table 1). 蹂 뿰援ъ뿉 솢슜븳 쑀쟾젙蹂대뒗 吏덈퀝愿由щ낯遺(KNIH) 샇꽌븰援먯뿉꽌 뿰援ъ쑄由 듅씤쓣 諛쏆 썑 遺꾩꽍쓣 닔뻾븯떎(1041231-170822-BR-062-01).

Basic characteristics of the subjects in the KARE

CharacteristicsTotal
Number of subjects8,840
Age (M years ± SD)52.22 ± 8.91
Gender [men (%) / women (%)]4182 (47) / 4658 (53)
Area [Anseong (%) / Ansan (%)]4205 (48) / 4635 (52)
Hemoglobin (M ± SD)13.58 ± 1.60
Hematocrit (M ± SD)41.02 ± 4.60

Abbreviations: KARE, Korean association resource; M, mean value; SD, standard deviation


븳援씤쓽 SNP 젙蹂대뒗 KARE 쑀쟾삎 옄猷뚮 湲곕컲쑝濡 븯떎. DNA 떆猷뚮뒗 뿰援 李몄뿬옄쓽 留먯큹삁븸뿉꽌 遺꾨━異붿텧븯怨, 쑀쟾삎 뙋룆쓣 쐞빐꽌뒗 Affymetrix Genome-Wide Human SNP array 5.0 (Affymetrix, Inc., Santa Clara, CA, USA)瑜 궗슜븯떎. 쑀쟾삎 뙋룆 젙솗룄媛 98% 씠븯씠嫄곕굹, 4% 씠긽쓽 넂 missing genotype call rate쓣 蹂댁씠嫄곕굹, 30% 珥덇낵쓽 heterozygosity瑜 媛吏嫄곕굹, 꽦蹂 遺덉씪移섍 議댁옱븯뒗 긽옄뱾 젣쇅릺뿀떎. SNP뱾쓽 뿼깋泥 긽쓽 쐞移섎뒗 UCSC Genome Browser on Human Feb. 2009 (GRCh37/ hg19)瑜 湲곗쑝濡 븯떎. 삉븳, 떎젣 떎뿕쟻쑝濡 SNP쓽 쑀쟾삎쓣 솗씤븳 寃 씠쇅뿉룄 빐떦릺뒗 쑀쟾醫뚯쐞 쁺뿭 뿉꽌뒗 MACH 1.0.16 (Li et al., 2010)瑜 궗슜븯뿬 異붽쟻쑝濡 imputation SNP쓣 諛쒓뎬븯뿬 遺꾩꽍뿉 궗슜븯떎. 蹂 뿰援ъ쓽 Imputation뿉 궗슜븳 湲곕낯 젙蹂대뒗 HapMap database (release 24) (International HapMap Consortium 2003)뿉꽌 以묎뎅씤(Han Chinese form Beijing)怨 씪蹂몄씤(Japanese in Tokyo)쓽 寃껋쓣 李멸퀬濡 吏꾪뻾븯떎.

遺遺꾩쓽 넻怨 遺꾩꽍뿉뒗 PLINK version 1.07 (http://pngu.-mgh.harvard.edu/~purcell/plink)怨 PASW Statistics version 18.0 (SPSS Inc. Chicago, IL, USA)쓣 궗슜븯떎. Hb怨 Hct뿉 븳 쑀쟾쟻 蹂씠쓽 긽愿꽦 遺꾩꽍 꽑삎 쉶洹 遺꾩꽍쓣 궗슜븯쑝硫 additive genetic model쓣 湲곕컲쑝濡 븯떎. 쉶洹遺꾩꽍쓽 떆뻾뿉 엳뼱꽌 굹씠, 吏뿭, 꽦蹂꾩쓣 怨듬닔濡 泥섎━븯뿬 遺꾩꽍븯떎. 遺꾩꽍 媛믪뿉 븳 쑀쓽닔以 0.05 誘몃쭔쓣 湲곗쑝濡 븯떎. 삉븳 遺꾩꽍 떆 湲곗씠 릺뒗 allele뒗 꽑뻾맂 뿰援ъ 룞씪븳 寃껋쑝濡 븯떎.

Zhong et al.뿉꽌 Hb 넻怨꾩쟻쑝濡 쑀쓽븳 SNP 26媛쒖쑝硫 Hct怨 넻怨꾩쟻쑝濡 쑀쓽븳 SNP 18媛쒖떎. 씠 SNP뱾쓣 븳援씤 肄뷀샇듃 SNP 젙蹂댁뿉꽌 솗씤빐 蹂댁븯쓣 븣, Hb뿉꽌뒗 26媛쒖쓽 SNP 以 21媛쒖쓽 SNP씠 遺꾩꽍 媛뒫븯떎. 삉븳 Hct뿉꽌뒗 18媛쒖쓽 SNP 以 12媛쒖쓽 SNP씠 遺꾩꽍뿉 궗슜릺뿀떎. 씠윭븳 諛⑹떇쑝濡 븳援씤 肄뷀샇듃뿉꽌 꽑蹂꾨맂 SNP뱾怨 Hb 냽룄, Hct 媛믪뿉 븳 긽愿꽦 遺꾩꽍쓣 吏꾪뻾븯떎(Table 2).

Replication results of linear regression analyses for RBC indices in Korean population and comparison of Fst for between two population

GeneSNPEAEuropeanKoreanFst


EAFbetaP-valueEAFbetaP-value

Hemoglobin
ATXN2rs10774625A0.4770.06121.44X10-90.0220.02750.6480.277
BRAPrs11065987G0.4190.06711.32X10-80.025-0.01630.7700.224
HIST1H1Ars9393681C0.4560.07176.95X10-110.7850.00060.9770.115
HIST1H1Crs9295685C0.4000.08874.11X10-130.737-0.00750.7040.116
HIST1H1Trs198833G0.1780.09709.48X10-100.0460.01420.7320.043
LRRC16rs17492120T0.1040.09691.65 X 10-80.037-0.00580.8990.017
MPSTrs5750373A0.4140.05812.10X10-80.6840.03620.0510.074
rs8141597C0.3470.06381.47 X 10-80.6590.02670.1440.097
PRKCErs10495928A0.6830.07447.58X10-100.8070.06503.08X10-32.01X10-2
PTPN11rs11066301G0.4270.06301.29 X 10-90.028-0.07090.1800.226
rs9348689T0.5520.08393.80X10-110.659-0.03570.0560.012
rs932316C0.4380.07884.76X10-90.1390.02040.4160.109
SCGNrs1321247T0.1760.12091.12 X 10-90.0340.02840.5500.054
rs2205936C0.5520.06869.15X10-90.730-0.01010.6040.034
rs9467556C0.1470.07939.61X10-90.1330.02670.2963.84X10-4
rs2235321A0.4240.06141.11X10-80.4940.08381.58X10-64.91X10-3
TMPRSS6rs5756505C0.4320.06393.99X10-100.4990.08371.30X10-64.52X10-3
rs855791G0.6120.09441.40X10-150.5060.08004.64X10-61.14X10-2
TRAFD1rs17630235A0.4100.06635.70X10-100.031-0.04560.3700.209
TRIM38rs12216125T0.3590.08101.55X10-110.1210.02150.4210.078
TSHZ2rs6013509G0.7500.06991.96 X 10-90.6610.01870.3089.63X10-3

Hematocrit

ATXN2rs10774625A0.4770.17024.88X10-100.0220.18590.2860.277
BRAPrs11065987G0.4190.18093.34X10-100.0250.13400.4090.224
rs69202110.7360.20966.96X10-110.6530.25691.21X10-68.19X10-3
HBS1Lrs9389268A0.7490.19781.60X10-100.6800.34511.53X10-105.83X10-3
rs9483788T0.7650.21723.55X10-110.6730.22473.38X10-51.04X10-2
PRKCErs10184620A0.9110.28347.23X10-90.9870.32590.1280.029
rs4953318A0.6270.20101.18X10-120.7780.23031.32X10-42.73X10-2
PTPN11rs11066301G0.4270.16473.97X10-90.028-0.10550.4910.226
SCGNrs9348689T0.5520.17821.28X10-80.659-0.13041.62X10-21.19X10-2
TFR2rs7385804C0.3780.15922.75X10-80.1340.01960.7910.078
TMPRSS6rs2413450C0.5810.16206.33X10-90.5000.18582.14X10-46.69X10-3
TRAFD1rs11066188A0.4100.17481.21 X 10-90.0310.04670.7530.209

The replicated SNPs are indicated in bold. Abbreviations: SNP, single nucleotide polymorphism; EA, effect allele; EAF, effect allele frequency; Fst, F-statistics


Hb 닔移섏쓽 긽愿꽦 遺꾩꽍뿉꽌 PRKCE (rs10495928), TMPRSS6 (rs2235321, rs5756505, rs855791) 쑀쟾옄쓽 SNP씠 쑀쓽븳 긽愿 愿怨(P<0.05)濡 굹궗떎(Table 2). 씠 SNP 以 rs5756505씠 Hb 닔移섏 媛옣 넂 쑀쓽닔以(P=1.30×10-6)쓣 蹂댁뿬二쇱뿀떎. 쑀읇씤 肄뷀샇듃 留덉갔媛吏濡 4 SNP Hb 닔移섏뿉 븳 effect allele瑜 蹂댁쑀븯怨 엳쓣닔濡 Hb 닔移섎 긽듅떆궎뒗 寃쏀뼢쓣 蹂댁뿬二쇱뿀떎.

Hct 닔移섏쓽 긽愿꽦 遺꾩꽍뿉꽌뒗 HBS1L (rs6920211, rs9389268, rs9483788), PRKCE (rs4953318), SCGN (rs9348689), TMPRSS6 (rs2413450) 쑀쟾옄쓽 SNP씠 쑀쓽븳 긽愿 愿怨(P<0.05)濡 굹궗떎(Table 2). 씠 SNP 以 rs9389268씠 Hct 媛믨낵 媛옣 넂 쑀쓽닔以(P=1.53×10-10)쓣 蹂댁뿬二쇱뿀떎. 븳렪 쑀읇씤 肄뷀샇듃뿉꽌 rs9348689 Hct 닔移섏뿉 븯뿬 effect allele瑜 蹂댁쑀븷닔濡 Hct 닔移섍 긽듅븯뒗 寃쏀뼢씠뿀吏留 븳援씤 肄뷀샇듃뿉꽌뒗 effect allele 蹂댁쑀븷닔濡 Hct 닔移섍 媛먯냼븯뒗 寃쏀뼢쑝濡 쑀쓽븳 寃곌낵媛 굹궗떎. 洹몃윭굹, 굹癒몄 5媛쒖쓽 SNP 쑀읇씤 肄뷀샇듃 留덉갔媛吏濡 effect allele瑜 蹂댁쑀븷닔濡 Hct 닔移섍 긽듅븯뒗 寃쏀뼢쑝濡 솗씤릺뿀떎.

옱쁽꽦쓣 蹂댁씠뒗 SNP뱾怨 洹몃젃吏 븡 SNP뱾 궗씠뿉 뼱뼚븳 李⑥씠媛 엳뒗吏瑜 궡렣蹂닿린 쐞빐 슦꽑쟻쑝濡 몢 媛쒖쓽 씤援 吏묐떒 媛꾩쓽 쑀쟾쟻 李⑥씠(Genetic distance)瑜 allele frequency濡 鍮꾧탳븯怨, 씠瑜 湲곕컲쑝濡 Fst 媛믪쓣 궛異쒗븯뿬 솗씤빐蹂댁븯떎. Fst 媛믪 V(q)/q(1-q)濡 怨꾩궛븯怨 씠 븣, V(q)뒗 쑀쟾옄삎鍮덈룄쓽 遺꾩궛媛믪씠怨 q뒗 쑀쟾옄삎쓽 weighted frequency瑜 굹궦떎. Fst뒗 0~1 궗씠쓽 媛믪쓣 媛吏硫 0뿉 媛源뚯슱닔濡 吏묐떒쓽 쑀쟾쟻 遺꾪솕媛 쟻寃 씪뼱궗쓬쓣 쓽誘명븯怨 媛믪씠 而ㅼ쭏닔濡 쑀쟾쟻 遺꾪솕媛 뜑 겕寃 씪뼱궗쓬쓣 쓽誘명븳떎. 슦꽑, 쑀쓽븳 寃곌낵濡 옱쁽맂 SNP뱾 쑀읇씤 肄뷀샇듃 븳援씤 肄뷀샇듃뿉꽌 effect allele frequency (EAF)媛 鍮꾩듂븳 鍮덈룄濡 솗씤릺뿀떎(Table 2). 諛섎㈃뿉, 옱쁽릺吏 븡 SNP뱾 옱쁽맂 SNP뱾怨 鍮꾧탳븯쓣 븣 쑀읇씤 肄뷀샇듃 븳援씤 肄뷀샇듃쓽 EAF 李⑥씠媛 遺꾨챸븯寃 겙 寃껋쓣 븣 닔 엳뿀쑝硫 겕寃뚮뒗 40% 씠긽 鍮덈룄쓽 李⑥씠媛 엳뒗 寃껋쓣 솗씤븯떎. 뵲씪꽌 쑀읇씤 肄뷀샇듃 븳援씤 肄뷀샇듃 궗씠쓽 씤醫 媛 쑀쟾쟻 李⑥씠쓽 젙룄瑜 Fst (F-statistics) 닔移섎줈 솗씤븯떎. Fst 닔移섎뒗 吏묐떒 媛 쑀쟾 蹂씠쓽 鍮덈룄瑜 湲곕컲쑝濡 븯뿬 쑀쟾쟻 李⑥씠瑜 굹궡뒗 媛믪쑝濡, 0.05 誘몃쭔씪 븣 吏묐떒 媛 쑀쟾쟻 嫄곕━媛 媛源뚯슫 寃껋쓣 굹궦떎. Hb 냽룄 Hct 媛믪뿉 빐 쑀쓽븳 寃곌낵濡 옱쁽맂 SNP뱾 Fst 媛믪씠 0.05 誘몃쭔쑝濡 솗씤릺뿀떎. TMPRSS6 쑀쟾옄 쓽 rs5756505씠 Hb 닔移섏뿉 빐 쑀쓽븳 寃곌낵瑜 굹궦 SNP 以 媛옣 쑀쟾쟻 李⑥씠媛 쟻 寃껋쑝濡 솗씤릺뿀떎(Fst= 4.52×10-3). 삉븳 Hct 닔移섏뿉 븳 遺꾩꽍뿉꽌뒗 HBS1L 쑀쟾옄쓽 rs9389268씠 媛옣 쑀쟾쟻 李⑥씠媛 쟻 寃껋쑝濡 솗씤릺뿀떎(Fst=5.83×10-3). 異붽쟻쑝濡 븳援씤 肄뷀샇듃뿉꽌 옱쁽맂 SNP, 옱쁽릺吏 븡 SNP쓽 Fst 媛믨낵 룊洹좎쓣 Hb, Hct 媛곴컖 룄몴濡 굹깉떎(Fig. 1). Hb쓽 寃곌낵 옱쁽맂 SNP쓽 룊洹 Fst 媛믪 0.010쑝濡 쑀쟾쟻 嫄곕━媛 媛源뚯슫 寃껋쑝濡 굹궗怨 옱쁽릺吏 븡 SNP쓽 룊洹 Fst 媛믪 0.100쑝濡 쑀쟾쟻 嫄곕━媛 떎냼 癒 寃껋쓣 솗씤뻽떎. Hct쓽 寃곌낵 룊洹 Fst 媛믪 옱쁽맂 SNP, 옱쁽릺吏 븡 SNP 媛곴컖 0.012, 0.174濡 솗씤릺뿀怨 Hb쓽 寃곌낵 鍮꾧탳뻽쓣 븣 옱쁽릺吏 븡 SNP뱾씠 긽쟻쑝濡 쑀쟾쟻 李⑥씠媛 뜑 엳뒗 寃껋쓣 븣 닔 엳뿀떎. 씠 寃곌낵瑜 넻빐 븳援씤쓣 긽쑝濡 Hb, Hct 뿰愿꽦씠 옱쁽맂 SNP쓣 諛쒓뎬븷 닔 엳뿀쑝硫 씠젃寃 옱쁽꽦쓣 蹂댁씤 SNP뱾 몢 씤醫 媛 由 쑀쟾옄 鍮덈룄쓽 李⑥씠媛 쟻떎뒗 寃껋쓣 븣 닔 엳뿀怨 옱쁽릺吏 븡 SNP뱾 몢 씤醫 媛 쑀쟾쟻 李⑥씠媛 긽쟻쑝濡 겙 寃껋쑝濡 솗씤릺뿀떎.

Fig. 1.

Fst result of between European population SNPs and Korean population SNPs. Mean Fst is line (A), line (B). The mean Fst value in hemoglobin results (A) is 0.010 for replicated SNPs and 0.100 for not replicated SNPs. The mean Fst value in hematocrit results (B) is 0.012 for replicated SNPs and 0.174 for not replicated SNPs. Above P value is t-test between mean Fst value. Abbreviations: SNP, single nucleotide polymorphism; Fst, F-statistics.


PRKCE, TMPRSS6뒗 Hb 냽룄 Hct 媛 紐⑤몢 쑀쓽븳 寃곌낵濡 옱쁽릺뿀떎. PRKCE뒗 protein kinase C epsilon 떒諛깆쭏쓣 諛쒗쁽븯怨 씠寃껋 洹쇱쑁 닔異뺤쓣 議곗젅븯怨 뿀삁꽦 넀긽 諛 떖옣 蹂댄샇쓽 以묒떖쟻씤 뿭븷쓣 븯뒗 寃껋쑝濡 븣젮졇 엳떎(Jideama et al., 1996). TMPRSS6 쑀쟾옄쓽 궛臾쇱씤 matriptase-2 hepcidin쓽 諛쒗쁽쓣 議곗젅븿쑝濡쒖뜥 泥좎쓽 빆긽꽦쓣 議곗젅븯怨 씠 쑀쟾옄쓽 蹂씠삎 삁옣 럹由ы떞, Hb, 泥좎쓽 怨쇰솕뿉 쁺뼢쓣 二쇰뒗 寃껋쑝濡 븣젮졇 엳떎(Gan et al., 2012; Capra et al., 2017). Hct 媛믪뿉 쑀쓽븳 寃곌낵濡 옱쁽맂 HBS1L Hb F 냽룄뿉 쁺뼢쓣 二쇨퀬 蹂씠삎 sickle cell disease瑜 쑀諛쒗븷 닔 엳쑝硫(Menzel and Thein 2019). SCGN 移쇱뒛 寃고빀 떒諛깆쭏씤 secretagogin쓣 諛쒗쁽븯뿬 꽭룷 利앹떇뿉 愿뿬븳떎.

理쒓렐 듅젙 吏덈퀝 삉뒗 몴쁽삎怨 쑀쟾쟻 떎삎꽦 궗씠뿉 긽愿 愿怨꾨 遺꾩꽍븯뿬 吏덈퀝 諛쒕퀝씠 쑀쟾쟻쑝濡 李⑥씠媛 엳쓣 닔 엳쓬쓣 젣떆븯뒗 뿰援щ뱾씠 솢諛쒗엳 吏꾪뻾릺怨 엳떎(Pandit et al., 2008; Choi et al., 2012; Wu et al., 2013; Jin et al., 2018; Ko and Jin, 2019). 씠踰 뿰援ъ뿉꽌 쟻삁援 닔移섏쓽 옱쁽꽦씠 솗씤맂 쑀쟾옄뱾뿉 븳 뿰援 삉븳 솢諛쒗엳 吏꾪뻾릺뼱 솕떎(Chen et al., 2013; Capra et al., 2017; Pinto et al., 2017; Menzel and Thein, 2019). 씠踰 뿰援щ뒗 湲곗〈뿉 쑀읇씤 肄뷀샇듃瑜 긽쑝濡 닔뻾븯뜕 쟻삁援 닔移섏 愿젴 엳뒗 쑀쟾옄쓽 쑀쟾쟻 떎삎꽦씠 븳援씤 肄뷀샇듃뿉꽌룄 룞씪븯寃 옱쁽릺뒗吏 솗씤븯怨 븯떎. 씠踰 뿰援ъ쓽 寃곌낵뒗 씪遺 쑀쟾옄뿉꽌 쑀쟾쟻 떎삎꽦怨 쟻삁援 닔移섏쓽 긽愿 愿怨꾧 씤醫낆뿉 뵲씪 李⑥씠媛 엳쓣 닔 엳떎뒗 寃껋쓣 留먰빐二쇨퀬 엳떎. 삉븳 븳援씤 긽쑝濡 Hb 냽룄 Hct 媛믪뿉 빐 긽愿 愿怨꾧 엳뒗 SNP쓣 솢슜븯뿬 삁븸愿젴 蹂듯빀吏덊솚쓽 씠빐 移섎즺 諛 삁諛⑹뿉 솢슜븷 닔 엳쓣 寃껋쑝濡 깮媛곷맂떎.

ACKNOWLEDGEMENT

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) grant to HS. J (NRF-2017R1D1A3B03034752) funded by the Ministry of Education. This study was conducted with bioresources from National Biobank of Korea, the Centers for Disease Control and Prevention, Republic of Korea (KBN-2017-046).

CONFLICT OF INTEREST

The authors declare that they have no competing interests.

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