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北印度儿童急性淋巴细胞白血病中杀伤细胞免疫球蛋白样受体与人类白细胞抗原I类的遗传关联

Genetic associations of killer immunoglobulin like receptors and class I human leukocyte antigens on childhood acute lymphoblastic leukemia among north Indians.

作者信息

Misra Maneesh Kumar, Prakash Swayam, Moulik Nirmalya Roy, Kumar Archana, Agrawal Suraksha

机构信息

Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India.

Division of Pediatric Hematology-Oncology, Department of Pediatrics, King George's Medical University, Lucknow 226003, Uttar Pradesh, India.

出版信息

Hum Immunol. 2016 Jan;77(1):41-46. doi: 10.1016/j.humimm.2015.10.009. Epub 2015 Oct 21.

Abstract

BACKGROUND

Molecular interactions between KIRs and their cognate HLA class-I ligands, play a central role in the regulation of natural killer (NK) cell responses in malignancies. We aimed to determine the role of KIR genes and their HLA ligands in genetic predisposition of childhood acute lymphoblastic leukemia (ALL).

METHODS

Genotyping of 16 KIR genes, along with HLA class-I groups C1/C2 and Bw4 super-type ligands, was carried-out in 137 childhood ALL cases and 274 healthy controls.

RESULTS

We observed an increased incidence of activating KIRs namely; 2DS2 (OR=2.23, p=<0.001), 2DS3 (OR=1.74, p=0.011), 3DS1 (OR=2.22, p=<0.001), 2DS5 (OR=2.10, p=0.001), 2DS1 (OR=4.42, p=<0.001) and 2DS4 (OR=2.88, p=<0.001) genes in childhood ALL cases compared to controls. Frequency of BB genotype that possess 2-6 activating KIR genes was predominant in cases compared to controls (OR=2.55, p=<0.001). KIR-receptor/HLA-ligand combinations analysis revealed a moderate risk of almost 2-fold for activating KIR-ligand combinations namely; KIR2DS1-HLAC2, KIR2DS2-HLAC1 and KIR3DS1-HLABw4 in childhood ALL cases.

CONCLUSION

Our data suggests the role for KIR genes and their HLA ligands in aetiology of childhood ALL.

摘要

背景

杀伤细胞免疫球蛋白样受体(KIR)与其同源的人类白细胞抗原(HLA)I类配体之间的分子相互作用,在恶性肿瘤中自然杀伤(NK)细胞反应的调节中起核心作用。我们旨在确定KIR基因及其HLA配体在儿童急性淋巴细胞白血病(ALL)遗传易感性中的作用。

方法

对137例儿童ALL病例和274例健康对照进行了16个KIR基因以及HLA I类C1/C2组和Bw4超型配体的基因分型。

结果

我们观察到激活型KIRs的发生率增加,即与对照组相比,儿童ALL病例中2DS2(比值比[OR]=2.23,p<0.001)、2DS3(OR=1.74,p=0.011)、3DS1(OR=2.22,p<0.001)、2DS5(OR=2.10,p=0.001)、2DS1(OR=4.42,p<0.001)和2DS4(OR=2.88,p<0.001)基因的发生率增加。与对照组相比,拥有2-6个激活型KIR基因的BB基因型在病例中占主导地位(OR=2.55,p<0.001)。KIR受体/HLA配体组合分析显示,在儿童ALL病例中,激活型KIR-配体组合(即KIR2DS1-HLAC2、KIR2DS2-HLAC1和KIR3DS1-HLABw4)的风险几乎增加了2倍。

结论

我们的数据表明KIR基因及其HLA配体在儿童ALL的病因学中起作用。

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