5-羟色胺1A受体、G蛋白β3亚基基因多态性与卒中后抑郁的相关性

Relationship between 5.hydroxytryptamine 1A receptor and G-protein β3 subunit polymorphisms and post-stroke depression

目的观察5-羟色胺1A受体（5-HTR1A）C（-1019）G基因与G蛋白β3亚基（GNβ3）基因C825T多态性在中国广州地区卒中后抑郁患者的分布情况及特点，探讨卒中后抑郁的遗传机制。方法选取159例首发脑卒中患者并根据汉密尔顿抑郁量表（HAMD）评分分为卒中后抑郁组（53例）和卒中对照组（106例），采用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）技术分析2组患者的5-HTR1AC（-1019）G和GN133C825T基因多态性。结果5-HTR1AC（-1019）G和GN[33C825T基因多态性在2组人群中的分布差异均有统计学意义，卒中后抑郁组5-HTR1A（-1019）GG基因型（8／53，15．1％）及G等位基因频率（44／106，41．5％）和GN[33825T等位基因频率（68／106，64．2％）均高于对照组（5／106，4．7％；35／212，16．5％；113／212，53．3％；x^2=23．204、23．655、3．392，均P〈0．05）。同时携带5-HTR1A（-1019）G和GN33825T等位基因者罹患卒中后抑郁的相对危险度（OR=4．980，95％CI2．429～10．210，P=0．00（3）比单独具有5-HTRIA（-1019）G等位基因者（OR=3．589，95％C12．113—6．096，P=0．000）或GN33825T等位基因者高（OR=0．638，95％C10．395～1．031，P=0．042）。结论5-HTR1AC（-1019）G和GN33C825T基因均可能是卒中后抑郁的易患基因，而且两者在卒中后抑郁的发病中存在微效协同作用。

Objective To assess whether 5-HTR1A C （ - 1019） G and GNβ3 C825T gene polymorphisms are associated with post-stroke depression （PSD） and explore the genetic mechanism of the pathogenesis of post-stroke depression. Methods All 159 patients with first stroke were divided into the PSD group and the control group according to HAMD scores. Their genotypes were determined with polymerase chain reaction and allele-specific restriction enzyme analysis. Results The frequency of 5- HTR1A （ - 1019） GG genotype （ 8/53,15.1% ）, G allele （44/106,41.5%） and GNβ3 825T allele （ 68/ 106,64. 2% ） were significantly higher in the post-stroke depression group than in the controls （5/106, 4. 7% ;35/212, 16. 5% ; 113/212, 53.3% ; x^2 = 23. 204, 23. 655, 3. 392, all P 〈 0. 05 ） . Combined genotype analysis showed that individuals with both 5-HTR1A （ - 1019 ） G and GNI33 825T allele （OR = 4. 980,95% CI 2. 429--10. 210,P =0. 000） had a higher risk than those with 5-HTR1A （ - 1019） G allele （ OR = 3. 589,95% CI 2. 113-6. 096, P = 0. 000 ） or GNβ825T allele （ OR = 0. 638,95% CI 0. 395- 1. 031 ,P =0. 042） only for post-stroke depression. Conclusion The 5-HTR1A C（ - 1019） G and GNβ3 C825T polymorphisms are predisposing genes of post-stroke depression. Our data also suggest a significant interaction between the 5-HTR1A （-1019） G allele and GNβ3 825T allele in post-stroke depression.