HLA-DP genetic variation, proxies for early life immune modulation and childhood acute lymphoblastic leukemia risk.
HLA-DP genetic variation, proxies for early life immune modulation and childhood acute lymphoblastic leukemia risk.
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DOI：
10.1182/blood-2012-01-404723
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发表时间：
2012-10
期刊：
影响因子：
20.3
通讯作者：
K. Urayama;A. Chokkalingam;C. Metayer;Xiaomei Ma;S. Selvin;L. Barcellos;J. Wiemels;J. Wiencke;Malcolm Taylor;P. Brennan;G. Dahl;P. Moonsamy;H. Erlich;E. Trachtenberg;P. Buffler
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作者：
K. Urayama;A. Chokkalingam;C. Metayer;Xiaomei Ma;S. Selvin;L. Barcellos;J. Wiemels;J. Wiencke;Malcolm Taylor;P. Brennan;G. Dahl;P. Moonsamy;H. Erlich;E. Trachtenberg;P. Buffler
人类白细胞抗原（HLA）基因是儿童急性淋巴细胞白血病（ALL）的候选遗传易感位点。我们研究了HLA-DP遗传变异对风险的影响，并评估了其与早期免疫调节的4个替代指标的潜在相互作用，包括婴儿期感染暴露（有哥哥姐姐、日托、耳部感染）和母乳喂养的测量。在HLA-DPA1和DPB1位点对585例ALL病例和848例对照进行基因分型。由于种族/民族的潜在异质性，我们只纳入了非西班牙裔白人（47%）和西班牙裔（53%）儿童，并在分析中分别考虑了这两个群体。Logistic回归分析显示，HLA-DPB1*01:01与ALL风险增加相关（优势比[OR] = 1.43, 95% CI, 1.01-2.04），西班牙裔无异质性（P = .969）。DPB1超型分析显示，儿童ALL与DP1显著相关，特别是高超二倍体ALL （OR = 1.83; 95% CI, 1.20-2.78）。在DP1和哥哥姐姐之间（P = 0.036）以及DP1和母乳喂养之间（P = 0.094）发现了相互作用的证据，两者都显示在低暴露类别中有统计学意义的DP1关联。这些发现支持在免疫系统调节不足的情况下，儿童ALL病因的免疫机制涉及HLA-DPB1基因。
The human leukocyte antigen (HLA) genes are candidate genetic susceptibility loci for childhood acute lymphoblastic leukemia (ALL). We examined the effect of HLA-DP genetic variation on risk and evaluated its potential interaction with 4 proxies for early immune modulation, including measures of infectious exposures in infancy (presence of older siblings, daycare attendance, ear infections) and breastfeeding. A total of 585 ALL cases and 848 controls were genotyped at the HLA-DPA1 and DPB1 loci. Because of potential heterogeneity in effect by race/ethnicity, we included only non-Hispanic white (47%) and Hispanic (53%) children and considered these 2 groups separately in the analysis. Logistic regression analyses showed an increased risk of ALL associated with HLA-DPB1*01:01 (odds ratio [OR] = 1.43, 95% CI, 1.01-2.04) with no heterogeneity by Hispanic ethnicity (P = .969). Analyses of DPB1 supertypes showed a marked childhood ALL association with DP1, particularly for high-hyperdiploid ALL (OR = 1.83; 95% CI, 1.20-2.78). Evidence of interaction was found between DP1 and older sibling (P = .036), and between DP1 and breastfeeding (P = .094), with both showing statistically significant DP1 associations within the lower exposure categories only. These findings support an immune mechanism in the etiology of childhood ALL involving the HLA-DPB1 gene in the context of an insufficiently modulated immune system.