PMID- 28398356
OWN - NLM
STAT- MEDLINE
DCOM- 20190311
LR  - 20221207
IS  - 1473-1150 (Electronic)
IS  - 1470-269X (Linking)
VI  - 18
IP  - 2
DP  - 2018 Apr
TI  - SNP-based HLA allele tagging, imputation and association with antiepileptic 
      drug-induced cutaneous reactions in Hong Kong Han Chinese.
PG  - 340-346
LID - 10.1038/tpj.2017.11 [doi]
AB  - Human leukocyte antigen (HLA) genes control the regulation of the human immune 
      system and are involved in immune-related diseases. Population surveys on 
      relationships between single nucleotide polymorphisms (SNP) and HLA alleles are 
      essential to conduct genetic association between HLA variants and diseases. 
      Samples were obtained from our in-house database for epilepsy genetics and 
      pharmacogenetics research. Using 184 epilepsy patients with both genome-wide SNP 
      array and HLA-A/B candidate gene sequencing data, we sought tagging SNPs that 
      completely represent sixHLA risk alleles; in addition, a Hong Kong 
      population-specific reference panel was constructed for SNP-based HLA imputation. 
      The performance of our new panel was compared to a recent Han Chinese panel. 
      Finally, genetic associations of HLA variants with mild skin rash were performed 
      on the combined sample of 408 patients. Common SNPs rs2571375 and rs144295468 
      were found to successfully tag HLA risk alleles A*31:01 and B*13:01, 
      respectively. HLA-B*15:02 can be predicted by rs144012689 with >95% sensitivity 
      and specificity. The imputation reference panel for the Hong Kong population had 
      comparable performance to the Han Chinese panel due to the large sample size for 
      common HLA alleles, though it retained discordance for imputing rare alleles. No 
      significant genetic associations were found between HLA genetic variants and mild 
      skin rash induced by aromatic antiepileptic drugs. This study provides new 
      information on the genetic structure of HLA regions in the Hong Kong population 
      by identifying tagging SNPs and serving as a reference panel. Moreover, our 
      comprehensive genetic analyses revealed no significant association between HLA 
      alleles and mild skin rash in Hong Kong Han Chinese.
FAU - Gui, H
AU  - Gui H
AD  - Center for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of 
      Hong Kong, Hong Kong SAR, China.
AD  - Center for Health Policy and Health Services Research, Henry Ford Health System, 
      Detroit, MI, USA.
FAU - Kwok, M
AU  - Kwok M
AD  - Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong 
      Kong SAR, China.
FAU - Baum, L
AU  - Baum L
AD  - Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong 
      Kong, Hong Kong SAR, China.
FAU - Sham, P C
AU  - Sham PC
AD  - Center for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of 
      Hong Kong, Hong Kong SAR, China.
AD  - Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong 
      Kong, Hong Kong SAR, China.
AD  - The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong 
      Kong, Hong Kong SAR, China.
FAU - Kwan, P
AU  - Kwan P
AD  - Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong 
      Kong SAR, China.
AD  - Departments of Medicine and Neurology, The University of Melbourne, Royal 
      Melbourne Hospital, Parkville, VIC, Australia.
FAU - Cherny, S S
AU  - Cherny SS
AD  - Center for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of 
      Hong Kong, Hong Kong SAR, China.
AD  - Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong 
      Kong, Hong Kong SAR, China.
AD  - The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong 
      Kong, Hong Kong SAR, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170411
PL  - United States
TA  - Pharmacogenomics J
JT  - The pharmacogenomics journal
JID - 101083949
RN  - 0 (Anticonvulsants)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Alleles
MH  - Anticonvulsants/*adverse effects
MH  - Asian People/*genetics
MH  - Databases, Genetic/statistics & numerical data
MH  - Epilepsy/drug therapy/epidemiology/genetics
MH  - Exanthema/*chemically induced/*genetics
MH  - Female
MH  - Genetic Association Studies/methods
MH  - HLA Antigens/*genetics
MH  - Hong Kong/epidemiology
MH  - Humans
MH  - Male
MH  - Polymorphism, Single Nucleotide/*genetics
EDAT- 2017/04/12 06:00
MHDA- 2019/03/12 06:00
CRDT- 2017/04/12 06:00
PHST- 2016/09/05 00:00 [received]
PHST- 2017/01/08 00:00 [revised]
PHST- 2017/02/14 00:00 [accepted]
PHST- 2017/04/12 06:00 [pubmed]
PHST- 2019/03/12 06:00 [medline]
PHST- 2017/04/12 06:00 [entrez]
AID - tpj201711 [pii]
AID - 10.1038/tpj.2017.11 [doi]
PST - ppublish
SO  - Pharmacogenomics J. 2018 Apr;18(2):340-346. doi: 10.1038/tpj.2017.11. Epub 2017 
      Apr 11.