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       환경 (설치)

    - python 2.7

    - centos 6.8

 

 

 

 

  • User's instruction 

 

 

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  HLA 유전자는 고형장기이식에서 ABO형 다음으로 중요한 유전자이다. 일반적으로 Class 1, Class 2, Class 3 유전자로 구분하며 Class 1 유전자는 Cytotoxic T cell이 바이러스에 감염된 세포나 종양세포를 인지하여 제거할 때 antigen recognition에 필수적이고,

 

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분류

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유전자

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Class 1

 

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Class 2

...


 

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Samples

Method

HLA-A

HLA-B

HLA-DRB1

NS1512240004

PCR-SBT

02:06

02:10

40:02

55:02

04:05

11:01

HLAreporter

02:10

02:10

40:02:01

55:02:01

04:05:01

11:01:01

HLAscan

02:06:01G

02:10

40:02:01

55:02:01G

04:05:01

11:01:01

NS1512240008

PCR-SBT

24:02

31:01

35:01

51:02

09:01

09:01

HLAreporter

24:82

31:01:02

35:42:02

51:02:02

09:01:02

09:01:02

HLAscan

24:02:01G

31:01:13

35:01:01G

51:02:01

09:01:02

09:01:02

NS1512240012

PCR-SBT

02:01

33:03

15:01

44:03

09:01

13:02

HLAreporter

02:01:01

33:03:01

15:01:01

44:03:11

09:01:02

13:02:01

HLAscan

02:01:01G

33:03:23

15:01:01G

44:03:01

09:01:02

13:02:01

NS1512240016

PCR-SBT

11:01

26:01

44:02:00

46:01

09:01

13:01

HLAreporter

11:01:01

26:01:01

44:02:01

46:01:01

09:01:02

13:01:01

HLAscan

11:01:01:01

26:01:01:01

44:02:01G

46:01:01

09:01:02

13:01:01

NS1512240020

PCR-SBT

02:01

02:06

13:01

40:02

08:02

12:02

HLAreporter

02:01:01

02:01:01

13:01:01

40:02:01

08:02:01

12:02:01

HLAscan

02:01:01G

02:06:01G

13:01:01

40:02:01

08:02:01

12:02:01

 

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Nomenclature DB 및 Haplotype 명명법

 

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Image Removed

  <그림   2> IMGT/HLA 데이터베이스 (http://www.ebi.ac.uk/ipd/imgt/hla/)   

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...

 

...

 

...

  

...

 

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...

 

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약물 부작용 (Adverse Drug Reaction; ADR) 및 질병 연관성

 

...

 

...

 

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약물과민반응증후군 (HSS/ DIHS/ DRESS)
피부약불이상반응 (SJS/ TEN)
간손상 (DILI)
무반응 (non-response)
 

...

 

   HLA-A, B, C, DQA1, DQB1, DRB1 등 haplotype의 종류가 다양한 HLA 유전자의 경우 약물 부작용 및 질병 위험이 다수 보고되어 있다. 각 HLA type에 따라 연관된 질병은 <표 5>, 약물 부작용은 <표 6>에 정리되어 있다.

    <표 5> HLA type 에 따른 질병 위험도 

유전자

type

질병명

질병명(영문)

위험도

출처

HLA-A

*01

중증근무력증

Myasthenia Gravis

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-A

*02

소아 특발성 관절염

Juvenile Idiopathic Arthritis

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-A

*29:02

맥락망막염증

Birdshot Chorioretinopathy

High risk

www.histocompatibilityandimmunogenetics.com

HLA-B

*08

중증근무력증

Myasthenia Gravis

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-B

*27

강직성 척추염

Ankylosing Spondylitis

High risk

PM_26613595

HLA-B

*27

소아 특발성 관절염

Juvenile Idiopathic Arthritis

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-B

*27

반응성 관절염

Reactive Arthritis

High risk

www.histocompatibilityandimmunogenetics.com

HLA-B

*27

포도막염

Uveitis

High risk

www.histocompatibilityandimmunogenetics.com

HLA-B

*27:02

척추염

Spondylitis

High risk

www.histocompatibilityandimmunogenetics.com

HLA-B

*27:05

척추염

Spondylitis

High risk

www.histocompatibilityandimmunogenetics.com

HLA-B

*51

베체트병

Behcet’s   Disease

High risk

PM_1280845

HLA-B

*60

강직성 척추염

Ankylosing Spondylitis

High risk

PM_1280845

HLA-C

*02

강직성 척추염

Ankylosing Spondylitis

risk

PM_26613595

HLA-C

*06

심상성건선

Psoriasis Vulgaris

High risk

www.histocompatibilityandimmunogenetics.com

HLA-C

*06:02

소아 특발성 관절염

Juvenile Idiopathic Arthritis

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQA1

*01:02

다발성 경화증

Multiple Sclerosis

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQA1

*01:02

쇼그렌 증후군

Sjogrens

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQA1

*01:02

전신홍반루푸스

Systemic Lupus Erythematosus

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQA1

*02:01

복강질환

Coeliac Disease

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQA1

*03

복강질환

Coeliac Disease

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQA1

*03:01

Graves병

Graves Disease

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQA1

*03:01

당뇨

Insulin Dependent Diabetes Mellitus

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQA1

*05:01

복강질환

Coeliac Disease

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQA1

*05:01

Graves병

Graves Disease

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQA1

*05:01

당뇨

Insulin Dependent Diabetes Mellitus

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQA1

*05:01

쇼그렌 증후군

Sjogrens

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQA1

*05:01

전신홍반루푸스

Systemic Lupus Erythematosus

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQB1

*02

애디슨병

Addison’s   Disease

risk

www.histocompatibilityandimmunogenetics.com

HLA-DQB1

*02:01

복강질환

Coeliac Disease

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQB1

*02:01

Graves병

Graves Disease

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQB1

*02:01

당뇨

Insulin Dependent Diabetes Mellitus

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQB1

*02:01

쇼그렌 증후군

Sjogrens

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQB1

*02:01

전신홍반루푸스

Systemic Lupus Erythematosus

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQB1

*02:02

복강질환

Coeliac Disease

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQB1

*03:02

애디슨병

Addison’s   Disease

risk

www.histocompatibilityandimmunogenetics.com

HLA-DQB1

*03:02

복강질환

Coeliac Disease

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQB1

*03:02

Graves병

Graves Disease

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQB1

*03:02

당뇨

Insulin Dependent Diabetes Mellitus

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQB1

*06:0

쇼그렌 증후군

Sjogrens

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQB1

*06:02

다발성 경화증

Multiple Sclerosis

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DQB1

*06:02

전신홍반루푸스

Systemic Lupus Erythematosus

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*01

류마티스 관절염

Rheumatoid Arthritis

High risk

PM_1280845

HLA-DRB1

*01:03

대장염

Colitis

risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*01:03

크론병

Crohn’s   Disease

risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*02

전신홍반루푸스

Systemic Lupus Erythematosis

High risk

PM_11092201

HLA-DRB1

*03

쇼그렌 증후군

Sjogrens Syndrome

High risk

PM_1864006

HLA-DRB1

*03

전신성 경화증

Systemic sclerosis

High risk

PM_11092201

HLA-DRB1

*03

전신홍반루푸스

Systemic Lupus Erythematosis

High risk

PM_11092201

HLA-DRB1

*03:01

애디슨병

Addison’s   Disease

risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*03:01

Graves병

Graves Disease

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*03:01

당뇨

Insulin Dependent Diabetes Mellitus

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*03:01

중증근무력증

Myasthenia Gravis

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*03:01

전신홍반루푸스

Systemic Lupus Erythematosus

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*04

류마티스 관절염

Rheumatoid Arthritis

High risk

PM_1280845

HLA-DRB1

*04

애디슨병

Addison’s   Disease

risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*04

소아 특발성 관절염

Juvenile Idiopathic Arthritis

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*04:01

Graves병

Graves Disease

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*04:01

당뇨

Insulin Dependent Diabetes Mellitus

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*04:07

광선가려움발진

Actinic Prurigo

High risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*06:02

기면증

Narcolepsy

High risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*07

크론병

Crohn’s

risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*07

중증근무력증

Myasthenia Gravis

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*08

소아 특발성 관절염

Juvenile Idiopathic Arthritis

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*10

류마티스 관절염

Rheumatoid Arthritis

High risk

PM_1280845

HLA-DRB1

*11

전신성 경화증

Systemic sclerosis

High risk

PM_11092201

HLA-DRB1

*11

소아 특발성 관절염

Juvenile Idiopathic Arthritis

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*15:01

다발성 경화증

Multiple Sclerosis

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*15:01

쇼그렌 증후군

Sjogrens Syndrome

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*15:01

전신홍반루푸스

Systemic Lupus Erythematosus

Low risk

www.histocompatibilityandimmunogenetics.com

HLA-DRB1

*52

다카야수 동맥염

Takayasu’s   Arteritis

High risk

PM_11092201

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            

 

<표 6>  HLA type 에 따른 약물 부작용 

유전자

type

Drug

용도

ADR

출처

HLA-A

*01:01

Carbamazepine

항간질약

HSS/DIHS/DRESS

PM_22920398

HLA-A

*02

Oxicam

해열진통제

SJS/TEN

PM_22920398

HLA-A

*02

Aminopenicillins

항생제

HSS/DIHS/DRESS

PMC4052542

HLA-A

*02:01

Amoxicillin?clavulanate

항균제

DILI

PM_22920398

HLA-A

*02:01

co-amoxiclav

항균제

DILI

PM_22920398

HLA-A

*05

Aminopenicillins

항생제

Delayed rash

PM_22920398

HLA-A

*11

Carbamazepine

항간질약

HSS/DIHS/DRESS

PM_22920398

HLA-A

*12

Oxicam

해열진통제

SJS/TEN

PM_22920398

HLA-A

*24:02

Methazolamide

탄산탈수소억제제

SJS/TEN

PM_22920398

HLA-A

*29

Sulphonamides

항균제

SJS/TEN

PM_22920398

HLA-A

*29

Sulphamethoxazole

항생제

SJS/TEN

PMC4052542

HLA-A

*30

Sulfamethoxazole

항균제

Fixed-drug eruption

PM_22920398

HLA-A

*30

Co-trimoxazole

항생제

Fixed drug eruptions

PMC4052542

HLA-A

*31:01

Carbamazepine

항간질약

SJS/TEN, Delayed rash

PM_22920398

HLA-A

*33:03

Ticlopidine

항혈소판제

DILI

PMC4052542

HLA-B

*08

D-penicillamine

단백뇨치료

Other

PM_22920398

HLA-B

*08

Gold sodium thiomalate

단백뇨치료, 혈소판감소증, 백혈구감소증 치료

Other

PM_22920398

HLA-B

*08

Clometacin

항염증제

DILI

PMC4052542

HLA-B

*08:01

Carbamazepine

항간질약

HSS/DIHS/DRESS

PM_22920398

HLA-B

*12

Sulphonamides

항균제

SJS/TEN

PM_22920398

HLA-B

*12

Sulphamethoxazole

항생제

SJS/TEN

PMC4052542

HLA-B

*13

Sulfamethoxazole

항균제

Fixed-drug eruption

PM_22920398

HLA-B

*13

Co-trimoxazole

항생제

Fixed drug eruptions

PMC4052542

HLA-B

*13:01

Phenytoin

항간질약

SJS/TEN

PM_22920398

HLA-B

*14

Nevirapine

바이러스치료제

HSS/DIHS/DRESS

PM_22920398

HLA-B

*15

Nevirapine

바이러스치료제

HSS/DIHS/DRESS

PM_22920398

HLA-B

*15:02

Carbamazepine

항간질약

SJS/TEN

PM_22920398

HLA-B

*15:02

Lamotrigine

항간질약

SJS/TEN

PM_22920398

HLA-B

*15:02

Oxcarbazepine

항간질약

SJS/TEN

PM_22920398

HLA-B

*15:02

Oxcarbazepine

항간질약

Delayed rash

PM_22920398

HLA-B

*15:02

Phenytoin

항간질약

SJS/TEN

PM_22920398

HLA-B

*15:11

Carbamazepine

항간질약

SJS/TEN

PM_22920398

HLA-B

*15:18

Carbamazepine

항간질약

SJS/TEN

PM_22920398

HLA-B

*15:18

Oxcarbazepine

항간질약

SJS/TEN

PM_22920398

HLA-B

*22

Feprazone

통증억제제

Fixed-drug eruption

PM_22920398

HLA-B

*27

Levamisole

구충제

Agranulocytosis

PM_22920398

HLA-B

*35:01

Nevirapine

바이러스치료제

HSS/DIHS/DRESS

PM_22920398

HLA-B

*35:05

Nevirapine

바이러스치료제

HSS/DIHS/DRESS

PM_22920398

HLA-B

*38

Clozapine

항정신병제

Agranulocytosis

PM_22920398

HLA-B

*38

Lamotrigine

항간질약

SJS/TEN

PM_22920398

HLA-B

*38

Sulfamethoxazole

항생제

SJS/TEN

PM_22920398

HLA-B

*51

Carbamazepine

항간질약

HSS/DIHS/DRESS

PM_22920398

HLA-B

*57:01

Abacavir

바이러스치료제

HSS/DIHS/DRESS

PM_22920398

HLA-B

*57:01

Flucloxacillin

항생제

DILI

PM_22920398

HLA-B

*58:01

Allopurinol

통풍치료제

SJS/TEN

PM_22920398

HLA-B

*58:01

Lamotrigine

항간질약

HSS/DIHS/DRESS

PMC4052542

HLA-B

*59:01

Carbamazepine

항간질약

SJS/TEN

PM_22920398

HLA-B

*59:01

Methazolamide

탄산탈수소억제제

SJS/TEN

PM_22920398

HLA-B

*73

Oxicam

해열진통제

SJS/TEN

PM_22920398

HLA-C

*01:02

Methazolamide

탄산탈수소억제제

SJS/TEN

PM_22920398

HLA-C

*04

Nevirapine

바이러스치료제

Delayed rash

PM_22920398

HLA-C

*04

Nevirapine

바이러스치료제

HSS/DIHS/DRESS

PM_22920398

HLA-C

*06

Sulfamethoxazole

항균제

Fixed-drug eruption

PM_22920398

HLA-C

*06

Co-trimoxazole

항생제

Fixed drug eruption

PMC4052542

HLA-C

*07:01

Carbamazepine

항간질약

HSS/DIHS/DRESS

PM_22920398

HLA-C

*07:04

Carbamazepine

항간질약

SJS/TEN

PM_22920398

HLA-C

*08

Nevirapine

바이러스치료제

HSS/DIHS/DRESS

PM_22920398

HLA-C

*08:01

Phenytoin

항간질약

SJS/TEN

PM_22920398

HLA-DPB1

*02:01

Aspirin

해열진통제

Other

PM_22920398

HLA-DPB1

*03:01

Aspirin

해열진통제

Other

PM_22920398

HLA-DQA1

*01:02

Lumiracoxib

항염증제

DILI

PM_22920398

HLA-DQA1

*02

Ximelagatran

항응고제

DILI

PM_22920398

HLA-DQA1

*02:01

Lapatinib

항암제

DILI

PM_22920398

HLA-DQA1

*05:01

Carbamazepine

항간질약

HSS/DIHS/DRESS

PM_22920398

HLA-DQB1

*01:03

Flucloxacillin

항생제

DILI

PM_22920398

HLA-DQB1

*02:01

Carbamazepine

항간질약

HSS/DIHS/DRESS

PM_22920398

HLA-DQB1

*02:02

Lapatinib

항암제

DILI

PM_22920398

HLA-DQB1

*06

Beryllium

폐질환치료제

Other

PM_22920398

HLA-DQB1

*06:02

Amoxicillin?clavulanate

항균제

DILI

PM_22920398

HLA-DQB1

*06:02

co-amoxiclav

항균제

DILI

PM_22920398

HLA-DQB1

*06:02

Lumiracoxib

항염증제

DILI

PM_22920398

HLA-DQB1

*06:09

Aspirin

해열진통제

Other

PM_22920398

HLA-DQB1

*06:09

Aspirin

해열진통제

HSS/DIHS/DRESS

PMC4052542

HLA-DQB1

6672C

Clozapine

항정신병제

Agranulocytosis

PM_22920398

HLA-DRB1

*01

D-penicillamine

단백뇨치료

Other

PM_22920398

HLA-DRB1

*01

Efavirenz

항균제

Delayed rash

PM_22920398

HLA-DRB1

*01

Nevirapine

바이러스치료제

Delayed rash

PM_22920398

HLA-DRB1

*01*07

Flucloxacillin

항생제

DILI

PM_22920398

HLA-DRB1

*01:01

Nevirapine

바이러스치료제

HSS/DIHS/DRESS

PM_22920398

HLA-DRB1

*01:02

Nevirapine

바이러스치료제

HSS/DIHS/DRESS

PM_22920398

HLA-DRB1

*03

D-penicillamine

단백뇨치료

Other

PM_22920398

HLA-DRB1

*03

Gold sodium thiomalate

단백뇨치료, 혈소판감소증, 백혈구감소증 치료

Other

PM_22920398

HLA-DRB1

*03

Gold-salt

류마티스치료제

non-response

PMC4052542

HLA-DRB1

*03:01

Carbamazepine

항간질약

HSS/DIHS/DRESS

PM_22920398

HLA-DRB1

*04

methotrexate+TNFα blocker

류마티스치료제

non-response

PM_26844284

HLA-DRB1

*04

Clozapine

항정신병제

Agranulocytosis

PM_22920398

HLA-DRB1

*04

Hydralazine

항고혈압제

Drug-induced lupus

 

erythematosis

PM_22920398

HLA-DRB1

*04

Isoniazid

항결핵제

Drug-induced lupus

 

...

...

PM_22920398

...

HLA-DRB1

...

*04

...

Methyldopa

...

항고혈압제

...

 

...

...

PM_22920398

...

HLA-DRB1

...

*04

...

Procainamide

...

항부정맥제

...

 

...

...

PM_22920398

...

HLA-DRB1

...

*04

...

Quinidine

...

항부정맥제

...

 

...

...

PM_22920398

...

HLA-DRB1

...

*04

...

Gold-salt

...

류마티스치료제

...

non-response

...

PMC4052542

...

HLA-DRB1

...

*05

...

Gold sodium thiomalate

...

단백뇨치료, 혈소판감소증, 백혈구감소증 치료

...

Other

...

PM_22920398

...

HLA-DRB1

...

*07

...

Sulphonamides

...

항균제

...

SJS/TEN

...

PM_22920398

...

HLA-DRB1

...

*07

...

Ximelagatran

...

항응고제

...

DILI

...

PM_22920398

...

HLA-DRB1

...

*07

...

Sulphamethoxazole

...

항생제

...

SJS/TEN

...

PMC4052542

...

HLA-DRB1

...

*07:01

...

Lapatinib

...

항암제

...

DILI

...

PM_22920398

...

HLA-DRB1

...

*11

...

NSAIDS

...

해열진통제

...

Other

...

PM_22920398

...

HLA-DRB1

...

*13

...

Beryllium

...

폐질환치료제

...

Other

...

PM_22920398

...

HLA-DRB1

...

*13

...

Diclofenac

...

해열진통제

...

DILI

...

PMC4052542

...

HLA-DRB1

...

*13:02

...

Aspirin

...

해열진통제

...

Other

...

PM_22920398

...

HLA-DRB1

...

*13:02

...

Aspirin

...

해열진통제

...

HSS/DIHS/DRESS

...

PMC4052542

...

HLA-DRB1

...

*15

...

Nevirapine

...

바이러스치료제

...

HSS/DIHS/DRESS

...

PM_22920398

...

HLA-DRB1

...

*15:01

...

Amoxicillin?clavulanate

...

항균제

...

DILI

...

PM_22920398

...

HLA-DRB1

...

*15:01

...

co-amoxiclav

...

항균제

...

DILI

...

PM_22920398

...

HLA-DRB1

...

*15:01

...

Lumiracoxib

...

항염증제

...

DILI

...

PM_22920398

...

HLA-DRB1

...

*16:02

...

Phenytoin

...

항간질약

...

SJS/TEN

...

PM_22920398

...

HLA-DRB1

...

*52

...

Aminopenicillins

...

바이러스치료제

...

Delayed rash

...

PM_22920398

...

HLA-DRB5

...

*01:01

...

Lumiracoxib

...

항염증제

...

DILI

...

PM_22920398