PMID- 23257407
OWN - NLM
STAT- MEDLINE
DCOM- 20130606
LR  - 20221207
IS  - 1477-0962 (Electronic)
IS  - 0961-2033 (Linking)
VI  - 22
IP  - 2
DP  - 2013 Feb
TI  - HLA variants rs9271366 and rs9275328 are associated with systemic lupus 
      erythematosus susceptibility in Malays and Chinese.
PG  - 198-204
LID - 10.1177/0961203312470183 [doi]
AB  - BACKGROUND: Human leukocyte antigen (HLA) antigens and genes have long been 
      reported associated with systemic lupus erythematosus (SLE) susceptibility in 
      many populations. With the advance in technologies such as genome-wide 
      association studies, many newly discovered SLE-associated single-nucleotide 
      polymorphisms (SNPs) have been reported in recent years. These include 
      HLA-DRB1/HLA-DQA1 rs9271366 and HLA-DQB1/HLA-DQA2 rs9275328. Our aim was to 
      investigate these SNPs in a Malaysian SLE cohort. MATERIALS AND METHODS: SNPs 
      rs9271366 and rs9275328 were screened across 790 Malaysian citizens from three 
      ethnic groups (360 patients and 430 healthy volunteers) by Taqman SNP genotyping 
      assays. Allele and genotyping frequencies, Hardy-Weinberg equilibrium, Fisher's 
      exact test and odds ratio were calculated for each SNP and ethnic group. Linkage 
      disequilibrium and interaction between the two SNPs were also evaluated. RESULTS: 
      The minor allele G and its homozygous genotype GG of HLA-DRB1/HLA-DQA1 rs9271366 
      significantly increased the SLE susceptibility in Malaysian patients, including 
      those of Malay and Chinese ethnicity (odds ratio (OR) > 1, p < 0.05). As for 
      HLA-DQB1/HLA-DQA2 rs9275328, the minor allele T and the heterozygous genotype CT 
      conferred protective effect to SLE in Malaysians, as well as in Malays and 
      Chinese, by having OR < 1 and p value <0.05. Both SNPs did not show associations 
      to SLE in Indians. D' and r (2) values for the two SNPs in LD analysis were 0.941 
      and 0.065, respectively, with haplotype GC and AT being significantly associated 
      with SLE (p < 5.0 x 10(-4)) after 10,000 permutations were performed. The MDR 
      test clustered the genotype combinations of GG and CC, and AG and CC of rs9271366 
      and rs9275328, accordingly, as high-risk group, and the two SNPs interacted 
      redundantly by removing 1.96% of the entropy. CONCLUSIONS: Our findings suggest 
      that in addition to some classical HLA variants, rs9271366 and rs9275328 are 
      additional polymorphisms worth considering in the Malaysian and possibly in a 
      larger Asian SLE scenario.
FAU - Chai, H C
AU  - Chai HC
AD  - Jeffrey Cheah School of Medicine and Health Sciences, Monash University (Sunway 
      Campus), Malaysia.
FAU - Phipps, M E
AU  - Phipps ME
FAU - Othman, I
AU  - Othman I
FAU - Tan, L P
AU  - Tan LP
FAU - Chua, K H
AU  - Chua KH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121220
PL  - England
TA  - Lupus
JT  - Lupus
JID - 9204265
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQA1 antigen)
RN  - 0 (HLA-DQA2 antigen)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Asian People
MH  - Genetic Predisposition to Disease
MH  - HLA-DQ Antigens/*genetics
MH  - HLA-DQ alpha-Chains/*genetics
MH  - HLA-DQ beta-Chains/*genetics
MH  - HLA-DRB1 Chains/*genetics
MH  - Humans
MH  - Lupus Erythematosus, Systemic/*ethnology/*genetics
MH  - Malaysia
MH  - Polymorphism, Single Nucleotide
EDAT- 2012/12/22 06:00
MHDA- 2013/06/07 06:00
CRDT- 2012/12/22 06:00
PHST- 2012/12/22 06:00 [entrez]
PHST- 2012/12/22 06:00 [pubmed]
PHST- 2013/06/07 06:00 [medline]
AID - 0961203312470183 [pii]
AID - 10.1177/0961203312470183 [doi]
PST - ppublish
SO  - Lupus. 2013 Feb;22(2):198-204. doi: 10.1177/0961203312470183. Epub 2012 Dec 20.