Overview of Genetic Testing in Korea: Curr

ent Status and Problematic Issues

Han-Wook Yoo, M.D., Ph.D.,

Medical Genetics Clinic & Laboratory, Department of Pediatrics, Asan Medical Center,
University of Ulsan College of Medicine, Seoul, Korea
 Company Logo

Outlines of Presentation

 Genetic testing: definition, classification

 Prerequisite for clinical DNA testing
 Current status of genetic testing in Korea
 DNA testing in single gene disorders
 DNA profiling
 Susceptibility DNA testing in Polygenic disorders
 Pharmacogenomic DNA testing
 Current issues of genetic testing in Korea
 Regulatory process of genetic testing in Korea
 Conclusion
 Company Logo

Classification & Definition of Genetic Testing

Testing DNA testing Molecular c Cytogenetic t Biochemical

yto-genetic esting genetic test
Purpose testing ing

DNA profiling Paternity testi

ng, Forensic in
vestigation

Disease diagnos Monogenic Me Micro-delet Chromosome Inborn erro

is (prenatal, pre ndelian disea ion & dupli numerical & r of metabo
symptomatic, ca se, Mitochondr cation synd structural dis lism
rrier testing) ial disease rome order

Disease predicti Cancer, DM, Al Maternal se

on zheimer disea rum screeni
(susceptibility & se, Hypertensi ng
resistance) on, Drug respo
nse
 Company Logo

Classification & Definition of Genetic Testing


 Clinical test: diagnostic testing, predictive testin
g, carrier testing, prenatal testing, preimplantati
on testing, newborn screening
Investigational test
Research test
 Company Logo

Prerequisite for clinically applicable DNA testing

Preferably single gene disorder

Known gene structure & function
Appropriate marker linked to morbid gene
Limited locus heterogeneity and genetic heterogeneity
Availability of genetic epidemiological data
Replacing or complementary for preexisting diagnostic test
Less cost-higher benefit
Sensitivity, specificity, positive & negative predictive values
Pre- & Post- test genetic counseling
 Maintenance of privacy and confidentiality

 Company Logo

DNA testing for single gene disorders in Korea

Number of laboratories
 5 Commercial laboratories
 >10 Institutional laboratories
Number of testing diseases
 3 to more than 50 monogenic diseases
Methods
 Medical DNA sequencing, DHPLC, PCR-RFLP, methyl
ation specific PCR, ASO hybridization, PCR-South
ern, genomic Southern, MLPA, real time PC
R, linkage analysis....
Reimbursement by national insurance (As of Jan-2008)
 Reimbursed in 17 tests (13 monogenic diseases,
3 familial cancer syndrome, 1 predictive testing)
 Regulated by price of ceiling in 62 tests (4
2 monogenic diseases, 12 oncogenes or tumor supp
ressor genes, 8 pharmacogenetic testings)
 Company Logo

Single Gene (Monogenic) Disorder

 Victor A. Mckusilk: Mendelian Inh

eritance in Man
 Online version of Mendelian Inhe
ritance in Man(OMIM)
 > 10,000 diseases or trait
 >2,500 human disease relate
d
 >2,000 loci mapped - mutatio
n (7% of total 29,000 genes)
 > 1500 genetic tests are avail
able.
 Company Logo

DNA testing for single gene disorders in Korea

Inherited metabolic disorders: urea cycle defects, Gaucher

disease, GSD Ia, Fabry disease, Wilson disase
Skeletal dysplasia: achondroplasia, osteogenesis imperf
ecta, craniosynostosis
Neuromuscular disorders: DMD/BMD, spinal muscular atro
phy
Triplet repeat expansion disorders: spinocerebellar ataxia,
fragile-X syndrome, myotonic dystrophy, Kennedy disease,
Huntington’s disease, DRPLA
Neurogenetic disorders: adrenoleukodystrophy, CADASIL,
dystonia
Hematologic disorders: hemophilia, factor V Leiden
 Company Logo

DNA testing for single gene disorders

Familial cancer syndromes: BRCA1, BRCA2, APC, Rb

Endocrine genetic disorder: MEN, congenital adrenal hyperp
lasia
Monogenic renal disorder: familial hyperuricemic nephropat
hy, nephrogenic DI

Monogenic eye disorder: corneal dystrophy

Dysmorphic syndromes: Prader-Willi/Angelman syndrome,
Rett syndrome, Holt-Oram syndrome, Marfan sydnrome

Mitochondrial disorders: MFLAS, MERRF, LHON, Kearn-Saye
rs syndrome, Leigh disease
 Company Logo

DNA testing for DNA profiling in Korea


 Forensic Medicine: National Institute of Scientific
Investigation, Department of Forensic Medicine i
n Medical Schools (>2)

Paternity testing: More than 10 commercial labor

atories
 Company Logo
SNP-based DNA testing for susceptibility genes
in polygenic disorders in Korea

Thrombophilia panel : Factor V Leiden in Caucacians, prothr

ombin(factor II), MTHFR (methylenetetrahydrofolate reduc
tase)
Coronary heart disease panel: lipoprotein (Lp(a), apoE), co
agulation factor, MTHFR
Hypertension : ACE
Insulin dependent diabetes mellitus : HLA
Cancer disease (non-familial) : tumor suppressor genes, on
cogenes (n-myc gene, breakpoint cluster region (bcr) (BCR
-ABL), breast cancer, colon cancer
Hemochromatosis : population screening for Caucacians
Alzheimer disease : familial vs sporadic (APOE genotyping)
Neural tube defect : MTHFR gene
 Company Logo

Pharmacogenomic DNA testing in Korea

Pharmacogenetic variants that have be

en significantly associated with drug re
sponse in at least two studies
(Nat Rev Genet 2003;4:937-947)
Company Logo
 Company Logo

Warfarin genotyping: CYP2C9 & VKORC1

 Company Logo

Current Issues of Genetic Testing in Korea (I)

 DTC (direct to consumer) or “Over the Counter” DNA testing

 More than 15 laboratories
 Advertised and sold over the Internet
 Limited oversight of the analytic & clinical validity of ge
netic tests
 No pre & post test genetic counseling

 Implementation of legislation
 Oversight of genetic testing laboratories
 Approval of diagnostic kits & methods
 Biomedical ethical-legal-social issues
 Company Logo

6. 유전자건강정보센터 (www.9191114.com/gene) – 검사종목

 Company Logo

Regulatory process of genetic testing (I)

 Initiated by Korean Society of Medical Genetics by reviewing most

commonly sold DTC tests on web sites
 Clinical validity evaluation by literature review and meta-analy
sis
 Publication of reports
 Implemented by the Ministry of Health & Welfare
 Funding a grant for research
 Organizing advisory committee of genetic testing composed of
expert physicians, geneticist, scientists, expert of bioethics, la
wyer, representative from NGO
 Holding a conference for public hearing
 Enhancing legislation by National Advisory Committee of “Bioe
thics & Security”
 Company Logo

Regulatory process of genetic testing (II)

 Since 2007-Jan, 14 DNA-based genetic tests are banned as a clinical test and 6 tests a
re limitedly allowed in specific clinical situation
 Prohibited DNA tests for clinical diagnostic purpose
 Hyperlipidemia related gene: LPL
 Hypertension related gene: Angiotensinogen
 Osteoporosis related genes: VDR, ER
 Diabete mellitus related genes: IRS-2. Mt16189
 Obesity related genes: UCP-1, Leptin, PPAR-gamma, ADRB3(B3AR)
 Alcoholism related gene: ALDH2
 Depression related gene: 5-HTT
 Longevity related gene: Mt5178A
 Intelligence related genes: IGF2R, CALL
Asthma related genes: IL-4, beta2-AR
Endurance related gene: ACE
Lung cancer related gene: CYP1A1
Violence related gene: SLC6A4
Curiosity related gene: DRD2. DRD4
 Company Logo

Regulatory process of genetic testing (III)

 limitedly allowed in specific clinical situation

  Ankylosing spondylitis related gene: HLA-B27
 Leukemia related genes: BCR/ABL
 Short stature related gene: SHOX
 Cancer related gene: P53
 Breast cancer genes: BRCA1, BRCA2
 Alzheimer related gene: Apolipoprotein E
 Any genetic tests for trait identification are prohibited.
 The banned genetic test will be reviewed and updated on a regular basis.
 Protection of genetic information privacy and informed consent should be
ensured.
 The DTC tests are strictly prohibited except DNA profiling for paternity test
ing.
 Pre & post-test genetic counseling and request for diagnostic DNA testing
should be offered exclusively by medical doctor.
 DNA-diagnostic kit is regulated by KFDA and law related medical practice.
 The introduction of positive system is currently being considered.
 Company Logo

Current Issues of Genetic Testing in Korea (II)

 Establishment of “Korea Institute of Genetic Testing Evaluation” in

2005
 Evaluation of clinical validity of genetic testing
 Quality assurance of genetic testing
 Enhancement of public & medical professionals’ awareness of pros
& cons of genetic testing by education
 Accreditation of genetic testing laboratories and personnel by Kor
ean Society of Medical Genetics
 Issues of insurance reimbursement
 Issues of certification & training program of medical geneticist as
a medical specialty
 Issues of oversight and regulation of DTC DNA testings
 Company Logo

Conclusion

 Genetic Testing in Korea

 “Medicalization”
 “Subspecialization”
 “Professionalization”
 “Molecularization”
 “Commercialization”
 “Cosumerization”
 SNP-based susceptibility genetic testing in polygenic
disorders
 Unproven clinical & analytical validities
 Unresolved ethical, legal, and social issues