HLA and KIR Associations of Cervical Neoplasia.
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Bao Xiao, Hanson Aimee L, Madeleine Margaret M, Wang Sophia S, Schwartz Stephen M, Newell Felicity, Pettersson-Kymmer Ulrika, Hemminki Kari, Tiews Sven, Steinberg Winfried, Rader Janet S, Castro Felipe, Safaeian Mahboobeh, Franco Eduardo L, Coutlée François, Ohlsson Claes, Cortes Adrian, Marshall Mhairi, Mukhopadhyay Pamela, Cremin Katie, Johnson Lisa G, Garland Suzanne M, Tabrizi Sepehr N, Wentzensen Nicolas, Sitas Freddy, Trimble Cornelia, Little Julian, Cruickshank Maggie, Frazer Ian H, Hildesheim Allan, Brown Matthew A, Duncan Emma L, Sun Ying Pu, Leo Paul J
Аннотация
METHODS: Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13858 healthy controls of European decent.
RESULTS: The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 × 10-9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10-8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10-9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10-5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006).
CONCLUSIONS: Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism.