The association between HLA DR, DQ antigens, and vulval lichen sclerosus in the UK: HLA DRB112 and its associated DRB112/DQB10301/04/09/010 haplotype confers susceptibility to vulval lichen sclerosus, and HLA DRB10301/04 and its associated DRB10301/04/DQB10201/02/03 haplotype protects from vulval lichen sclerosus.
Lichen sclerosus (LS) is considered to have an immunogenetic background. Several small studies, using serological typing, have reported that HLA-DR11, DR12, and DQ7 were increased in LS, with DR17 less frequent. This study aimed to validate and detect new HLA-DR and DQ associations with LS in females and its characteristic clinical parameters. The cases, 187 female LS patients, and 354 healthy controls were all UK North Europeans. PCR-sequence specific primers method was applied to genotype the HLA-DR, DQ polymorphisms that correspond to 17 serologically defined DR and seven DQ antigens. Statistical analysis was performed with two-tailed Fisher's exact test with Bonferroni adjustment (p value after Bonferrroni adjustment, Pc). We found increased frequency of DRB1*12 (DR12) (11.2%vs 2.5%, pc < 0.01) and the haplotype DRB1*12/DQB1*0301/04/09/010 (11.2%vs 2.5%, p < 0.001, pc < 0.05), and a lower frequency of DRB1*0301/04 (DR17) (11.8%vs 25.8%, pc < 0.01) and the haplotype DRB1*03/DQB1*02DRB1*0301/DQB1*0201/02/03 (11.2%vs 24.6%, pc < 0.0001) in patients compared with controls. HLA DR and DQ antigens were not associated with time of onset of disease, site of involvement, structural changes of genitals, and response to treatment with potent topical steroids. In conclusion, HLA-DR and DQ antigens or their haplotypes appear to be involved in both susceptibility to and protection from LS.
Gao
Xing-Hua
XH
Department of Dermatology, No. 1 Hospital of China Medical University, Shenyang, China. gaobarry@hotmail.com
Barnardo
Martin C M N
MC
Winsey
Samantha
S
Ahmad
Tariq
T
Cook
Julia
J
Agudelo
Juliet D
JD
Zhai
Ning
N
Powell
Jenny J
JJ
Fuggle
Susan V
SV
Wojnarowska
Fenella
F
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D005260:Female; D005787:Gene Frequency; D006683:HLA-DQ Antigens / Q000032:analysis / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000032:analysis / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013256:Steroids / Q000627:therapeutic use; D006113:United Kingdom; D014844:Vulva / Q000276:immunology / Q000473:pathology; D007724:Vulvar Lichen Sclerosus / Q000235:genetics* / Q000276:immunology / Q000473:pathology
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D008562:Membrane Glycoproteins; D013256:Steroids