Association of the genetic diversity of killer cell immunoglobulin-like receptor genes and HLA-C ligand in Saudi women with breast cancer

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• 作者：Suliman Y. Alomar ; Afrah Alkhuriji ; Paul Trayhyrn ; Abdulkarim Alhetheel…
• 关键词：Genetic association ; HLA ligands ; Malignant diseases ; Natural killer cells
• 刊名：Immunogenetics
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：69
• 期：2
• 页码：69-76
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Immunology; Human Genetics; Gene Function; Cell Biology; Allergology;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-1211
• 卷排序：69

文摘

Breast cancer (BC) progression and metastases have been linked to antitumor immunity inefficiency and particularly to natural killer (NK) cells. Killer cell immunoglobulin-like receptors (KIRs) are the most polymorphic receptors of NK cells. Through their interactions with human leukocyte antigen (HLA)-C ligands, they modulate NK and T cell actions against target cells. Therefore, we studied the combinatorial effect of KIR genes and their HLA-C ligands on the susceptibility to development of BC in Saudi women. The presence of KIR genes and HLA-C1 and HLA-C2 groups was typed in 50 Saudi patients living in Riyadh and 65 healthy controls using polymerase chain reaction with sequence-specific primers. Our results indicated a protective effect by the KIR2DS2, 2DS3, and 2DL5A genes against BC (OR = 0.25, 0.21, and 0.27, respectively, and p < 0.01). The synergistic action of the three genes was observed when they occurred together, and the absence of the three genes increased BC occurrence by 6.5-fold. Distribution of the HLA-C1/C2 ligand between patients and controls showed an increase in the risk of BC occurrence for the heterozygote C1/C2 (OR = 2.33; 95 % CI = 1.08–5.02; p = 0.037) and a protective effect of the homozygote C2C2 (OR = 0.03; 95 % CI = 0.009–0.098; p < 0.001). Combinatory analyses of KIR genes and their HLA-C ligands showed protective effects of KIR2DL2 and 2DL3 in the absence of their HLA-C1 ligand. These results suggested that KIR-gene content combined with their ligand could influence the risk of BC development in women in Saudi Arabia.