Al-Absi Boshra, Razif Muhammad F M, Noor Suzita M, Saif-Ali Riyadh, Aqlan Mohammed, Salem Sameer D, Ahmed Radwan H, Muniandy Sekaran
1 Department of Molecular Medicine, University of Malaya , Kuala Lumpur, Malaysia .
2 Department of Biomedical Science, Faculty of Medicine, University of Malaya , Kuala Lumpur, Malaysia .
Genet Test Mol Biomarkers. 2017 Oct;21(10):592-599. doi: 10.1089/gtmb.2017.0084. Epub 2017 Aug 2.
Genome-wide and candidate gene association studies have previously revealed links between a predisposition to acute lymphoblastic leukemia (ALL) and genetic polymorphisms in the following genes: IKZF1 (7p12.2; ID: 10320), DDC (7p12.2; ID: 1644), CDKN2A (9p21.3; ID: 1029), CEBPE (14q11.2; ID: 1053), and LMO1 (11p15; ID: 4004). In this study, we aimed to conduct an investigation into the possible association between polymorphisms in these genes and ALL within a sample of Yemeni children of Arab-Asian descent.
Seven single-nucleotide polymorphisms (SNPs) in IKZF1, three SNPs in DDC, two SNPs in CDKN2A, two SNPs in CEBPE, and three SNPs in LMO1 were genotyped in 289 Yemeni children (136 cases and 153 controls), using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic Array). Logistic regression analyses were used to estimate ALL risk, and the strength of association was expressed as odds ratios with 95% confidence intervals.
We found that the IKZF1 SNP rs10235796 C allele (p = 0.002), the IKZF1 rs6964969 A>G polymorphism (p = 0.048, GG vs. AA), the CDKN2A rs3731246 G>C polymorphism (p = 0.047, GC+CC vs. GG), and the CDKN2A SNP rs3731246 C allele (p = 0.007) were significantly associated with ALL in Yemenis of Arab-Asian descent. In addition, a borderline association was found between IKZF1 rs4132601 T>G variant and ALL risk. No associations were found between the IKZF1 SNPs (rs11978267; rs7789635), DDC SNPs (rs3779084; rs880028; rs7809758), CDKN2A SNP (rs3731217), the CEBPE SNPs (rs2239633; rs12434881) and LMO1 SNPs (rs442264; rs3794012; rs4237770) with ALL in Yemeni children.
The IKZF1 SNPs, rs10235796 and rs6964969, and the CDKN2A SNP rs3731246 (previously unreported) could serve as risk markers for ALL susceptibility in Yemeni children.
全基因组关联研究和候选基因关联研究此前已揭示急性淋巴细胞白血病（ALL）易感性与以下基因中的遗传多态性之间的联系：IKZF1（7p12.2；ID：10320）、DDC（7p12.2；ID：1644）、CDKN2A（9p21.3；ID：1029）、CEBPE（14q11.2；ID：1053）和LMO1（11p15；ID：4004）。在本研究中，我们旨在调查这些基因中的多态性与阿拉伯 - 亚洲血统的也门儿童样本中ALL之间的可能关联。
使用纳米流体动态阵列（Fluidigm 192.24动态阵列）对289名也门儿童（136例病例和153名对照）进行IKZF1中的7个单核苷酸多态性（SNP）、DDC中的3个SNP、CDKN2A中的2个SNP、CEBPE中的2个SNP和LMO1中的3个SNP的基因分型。采用逻辑回归分析估计ALL风险，关联强度以95%置信区间的优势比表示。
我们发现IKZF1 SNP rs10235796的C等位基因（p = 0.002）、IKZF1 rs6964969 A>G多态性（p = 0.048，GG与AA相比）、CDKN2A rs3731246 G>C多态性（p = 0.047，GC + CC与GG相比）以及CDKN2A SNP rs3731246的C等位基因（p = 0.007）与阿拉伯 - 亚洲血统的也门人患ALL显著相关。此外，发现IKZF1 rs4132601 T>G变异与ALL风险之间存在临界关联。在也门儿童中，未发现IKZF（rs11978267；rs7789635）、DDC（rs3779084；rs880028；rs7809758）、CDKN2A SNP（rs3731217）、CEBPE（rs2239633；rs12434881）和LMO1（rs442264；rs3794012；rs4237770）的SNP与ALL之间存在关联。
IKZF1的SNP rs10235796和rs6964969以及CDKN2A的SNP rs3731246（此前未报道）可作为也门儿童ALL易感性的风险标志物
