靜脈曲張病患的全基因關聯性研究

A Genome-wide Association Study in Patients of Varicose Veins

李孟霖(Meng-Lin Lee)

指導教授 ： 廖光文 ； 黃憲達

國立交通大學/生物科技學院/生物科技學系暨研究所/博士(2020年)

摘要

背景:
靜脈曲張在他的致病機轉上已經知道基因佔有一個重要的角色。然而，確切的致病機轉仍不清楚。這個研究主要是要比較一組靜脈曲張病患和健康族群的基因資訊，並希望從中發現與該疾病相關的特定有意義的基因關聯性。

方法:
我們將一群以血管超音波診斷靜脈曲張並接受過手術的病患納入研究。並蒐集其基本的臨床病徵及人口統計學資料。我們採用Infinium HumanCoreExome-24 生物晶片(Illumina, US; rename to Infinium CoreExome-24 afterwards)來檢測其基因資訊並與蒐集自台灣生物基因資料庫的一千名健康族群對照組之基因資訊做比較。之後我們進一步將病患以各式臨床及超音波的參數做分組並將其基因資訊檢測及做小組內比較。

結果:
總共蒐集了96位病患及其基因資訊。其中66位為女性，30位為男性。平均年紀為61.7±1.1歲。其中39位為CEAP分級2-3級，57位為CEAP分級4-6級。在分析比較96位病患及1000名健康對照組之後，發現2個顯著的單核甘酸多態性變異點位分別位在DPYSL2及VSTM2L基因上。在分析比較39位C2-3病患及57位C4-6病患後，發現4個顯著的單核甘酸多態性變異點位分別位在ZNF664-FAM101A, PHF2, ACOT,及TOM1L1基因上。在使用各式超音波參數做小組分析後，我們發現其他10個顯著的單核甘酸多態性變異點位。其中，有兩個點位位於同一個SLC14A2基因上。其餘的8個基因分別為KCNIP4, IFLTD1, COL15A1, ESRRB, LRRK2, GLIS3, ACPT及EYA2基因。

結論:
我們的初步結果發現16個顯著單核甘酸多態性變異點位分別對應在15個基因上。每一個點位及其對應的基因產物都值得進一步的研究，尤其是點位重複出現的SLC14A2基因。

關鍵字

單核甘酸多態性變異 ； 全基因體關聯性研究

並列摘要

Background:
Varicose vein disease is well-known for a genetic role in its pathogenesis. However, the exact mechanisms are still far from clear. The aim of this study was to compare the genetic information between a group of varicose vein patients and healthy controls and to identify certain significant genetic associations with the disease.

Methods:
A cohort of varicose vein patients, diagnosed with ultrasound examination and received surgery in our hospital, were recruited. Basic clinical characteristics and demographics were collected. Their genetic information was examined using Infinium HumanCoreExome-24 Beadchip (Illumina, US; rename to Infinium CoreExome-24 afterwards) and compared to the genetic information of one-thousand gender-matched healthy controls from Taiwan Biobank database. Then we divided these patients into two subgroups by clinical and ultrasound parameters. The genetic information was examined and compared accordingly.

Results:
A total of ninety-six varicose vein patients and their genetic information were collected. There were sixty-six women and thirty men. The average age was 61.7±1.1 years old. There were thirty-nine patients of CEAP class 2 to 3 (C2-3), and fifty-seven patients of CEAP class 4 to 6 (C4-6). After comparing the genetic information of ninety-six patients to that of healthy controls, there were two significant single nucleotide polymorphisms (SNPs) located on DPYSL2 and VSTM2L genes. After comparing the genetic information of thirty-nine C2-3 patients to that of fifty-seven C4-6 patients, there were four significant SNPs located on ZNF664-FAM101A, PHF2, ACOT, and TOM1L1 genes, respectively. By applying various ultrasound parameters for the subgroup analysis, we have identified another ten significant SNPs. Among them, two SNPs were located on the same gene named SLC14A2. The residual eight genes’ name were KCNIP4, IFLTD1, COL15A1, ESRRB, LRRK2, GLIS3, ACPT, and EYA2, respectively.

Conclusions:
Our preliminary result identified a total of sixteen significant SNPs located on fifteen corresponding genes. All of them and their corresponding genetic products may warrant further investigations, especially the repeated SLC14A2 gene.

並列關鍵字

Single Nucleotide Polymorphism ； Genome-wide association study

參考文獻

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