OR2T3基因与动脉性肺动脉高压的关联性分析

Association between OR2T3 gene and pulmonary arterial hypertension

目的寻找动脉性肺动脉高压（PAH）的致病基因并验证OR2T3基因与PAH的关联性。方法对两个PAH家系中的4例患者和1名正常对照进行全外显子测序，利用生物信息学分析和组间比较，筛选出患者特有的变异，并对筛选出的变异使用Sanger测序法在30例特发性肺动脉高压患者、90例健康对照和30例慢性血栓栓塞性肺动脉高压患者中基因分型验证，进一步分析变异与PAH的相关性。结果全外显子组测序筛选到57个变异可能与PAH疾病相关。57个变异中OR2T3rs18748995变异在30例特发性肺动脉高压患者中存在6例AG杂合子，而在两家系其余健康人（AⅠ-1，AⅡ-3和BⅡ-1）及90例健康对照中未发现G等位基因携带者，差异有统计学意义（P〈0．05）；在30例慢性血栓栓塞性肺动脉高压患者中亦未发现该变异。结论OR2T3基因可能是PAH的致病基因，OR2T3rs148748995可能与PAH关联。

Objective To explore the pathogenic genes of pulmonary arterial hypertension （PAH） and validate the association between OR2T3 gene and PAH. Methods Whole exome sequencing was performed in four patients and one healthy person as control in two pulmonary arterial hypertension pedigree; patient-specific variations were screened by bioinformatics methods and comparison between groups. To further analyze the association between these variations and PAH, Sanger sequencing was used to analyze the genotype of patient-specific variations of 30 patients with idiopathic PAH, 90 healthy people and 30 patients with chronic thromboembolic pulmonary hypertension. Results The preliminary findings of whole exome sequencing were 57 variations may be associated with PAH; Among them, there were 6 AG heterozygotes due to OR2T3rs148748995 in the 30 idiopathic PAH patients, while no G allele carrier was found in other healthy people of two pulmonary arterial hypertension pedigree （ A Ⅰ -1, A Ⅱ -3, B Ⅱ-1 ） and 90 normal control, and the difference was statistically significant （P 〈 0. 05 ）. The variation also didn＇t exist in 30 chronic thromboembolic pulmonary hypertension patients. Conclusion OR2T3 gene may be the pathogenic gene of PAH and OR2T3rs148748995 could have a role in the development of PAH.