Kappelman Michael D, Lange Aksel, Randell Rachel L, Basta Patricia V, Sandler Robert S, Laugesen Kristina, Byrjalsen Anna, Christensen Tina, Frøslev Trine, Erichsen Rune
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
Clin Epidemiol. 2018 Feb 28;10:215-222. doi: 10.2147/CLEP.S143322. eCollection 2018.
Epidemiologic studies combining exposure and outcome data with the collection of biosamples are needed to study gene-environment interactions that might contribute to the etiology of complex diseases such as pediatric Crohn's disease (CD). Nationwide registries, including those in Denmark and other Scandinavian countries, provide efficient and reliable sources of data for epidemiological studies evaluating the environmental determinants of disease. We performed a pilot study to test the feasibility of collecting salivary DNA to augment registry data in established cases of pediatric CD and randomly selected, population-based controls.
Cases of CD born after 1995 and residing in the central region of Denmark were identified through the Danish National Patient Registry and confirmed by using standard diagnostic criteria. Age- and gender-matched controls were selected at random through the civil registration system. Cases and controls were contacted by mail and telephone and invited to submit a saliva sample. DNA was extracted and genotyped for six CD-associated single-nucleotide polymorphisms (SNPs).
A total of 53 cases of pediatric CD were invited, and 40 contributed a saliva sample (75% response rate). A total of 126 controls were invited, and 54 contributed a saliva sample (44% response rate). As expected, demographic characteristics did not differ between cases and controls. DNA was successfully isolated from 93 of 94 samples. Genotyping was performed with only 2% undetermined genotypes. For five of six SNPs known to be associated with CD, risk allele frequencies were higher in cases than controls.
This pilot study strongly supports the feasibility of augmenting traditional epidemiological data from Danish population-based registries with the de novo collection of genetic information from population-based cases and controls. This will facilitate rigorous studies of gene-environment interactions in complex chronic conditions such as CD.
需要开展将暴露与结局数据和生物样本采集相结合的流行病学研究，以探究可能导致诸如儿童克罗恩病（CD）等复杂疾病病因的基因-环境相互作用。包括丹麦及其他斯堪的纳维亚国家在内的全国性登记系统，为评估疾病环境决定因素的流行病学研究提供了高效且可靠的数据来源。我们开展了一项试点研究，以测试在已确诊的儿童CD病例及随机选取的基于人群的对照中收集唾液DNA以扩充登记数据的可行性。
通过丹麦国家患者登记系统识别出1995年后出生且居住在丹麦中部地区的CD病例，并采用标准诊断标准进行确诊。通过民事登记系统随机选取年龄和性别匹配的对照。通过邮件和电话联系病例与对照，并邀请他们提交唾液样本。提取DNA并对六个与CD相关的单核苷酸多态性（SNP）进行基因分型。
共邀请了53例儿童CD病例，40例提供了唾液样本（应答率75%）。共邀请了126名对照，54名提供了唾液样本（应答率44%）。正如预期，病例与对照的人口统计学特征并无差异。94个样本中有93个成功分离出DNA。基因分型时未确定基因型的比例仅为2%。对于六个已知与CD相关的SNP中的五个，病例组中风险等位基因频率高于对照组。
这项试点研究有力地支持了通过从基于人群的病例和对照中重新收集遗传信息来扩充丹麦基于人群登记系统的传统流行病学数据的可行性。这将有助于对诸如CD等复杂慢性病中的基因-环境相互作用进行严谨研究。
