Chua Kek Heng, Lian Lay Hoong, Khor Wei Ching, Lee Way Seah, Hilmi Ida, Goh Khean Lee, Kee Boon Pin
Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
J Dig Dis. 2015 Apr;16(4):205-16. doi: 10.1111/1751-2980.12229.
The study aimed to investigate the association between the interferon regulatory factor 5 (IRF5) gene polymorphisms and the onset of Crohn's disease (CD) in a Malaysian cohort.
Genomic DNA was extracted from blood samples collected from 91 CD patients and 100 healthy individuals via a conventional phenol-chloroform extraction method. Screening of the four target single nucleotide polymorphisms (SNPs), including rs3807306, rs4728142, rs10954213 and rs11770589 was carried out in a real-time polymerase chain reaction (PCR) thermal cycler using TaqMan genotyping assay. The genetic data obtained was subsequently subjected to statistical analysis to relate the SNPs to the onset of CD in the Malaysian population. The genotyping assay and data were further validated selectively by conventional PCR amplification of the SNP sites and DNA sequencing.
The rs3807306 G allele was a risk factor for CD (OR 2.3630, P = 0.00004), whereas the homozygous T genotype was protective against the disease (OR 0.2038, P = 0.00004). The heterozygous A/G genotype of rs10954213 was significantly associated with CD (OR 4.319, P = 0.0377). On the other hand, the homozygous A and heterozygous A/G genotypes of the rs11770589 were significant in the controls (OR 0.4242, P = 0.0166) and patients (OR 2.000, P = 0.0179), respectively. In the ethnic-stratification analysis, the rs11770589 homozygous A genotype was protective in Indians (OR 0.1551, P = 0.0112).
IRF5 gene polymorphisms may play a role in the development of CD in the Malaysian population.
本研究旨在调查马来西亚人群中干扰素调节因子5（IRF5）基因多态性与克罗恩病（CD）发病之间的关联。
采用传统的酚-氯仿提取法从91例CD患者和100名健康个体采集的血液样本中提取基因组DNA。使用TaqMan基因分型检测法在实时聚合酶链反应（PCR）热循环仪中对包括rs3807306、rs4728142、rs10954213和rs11770589在内的四个目标单核苷酸多态性（SNP）进行筛查。随后对获得的遗传数据进行统计分析，以确定这些SNP与马来西亚人群中CD发病的关系。通过对SNP位点进行常规PCR扩增和DNA测序，对基因分型检测和数据进行选择性进一步验证。
rs3807306的G等位基因是CD的危险因素（比值比2.3630，P = 0.00004），而纯合T基因型对该病具有保护作用（比值比0.2038，P = 0.00004）。rs10954213的杂合A/G基因型与CD显著相关（比值比4.319，P = 0.0377）。另一方面，rs11770589的纯合A基因型和杂合A/G基因型分别在对照组（比值比0.4242，P = 0.0166）和患者组（比值比2.000，P = 0.0179）中具有显著性。在种族分层分析中，rs11770589的纯合A基因型对印度人具有保护作用（比值比0.1551，P = 0.0112）。
IRF5基因多态性可能在马来西亚人群CD的发生发展中起作用。
