PDF(Pubmed)
Abstract：
UNASSIGNED: Depression and coronary heart disease (CHD) have common risk mechanisms. Common single nucleotide polymorphisms (SNPs) may be associated with the risk of depression combined with coronary heart disease.
UNASSIGNED: This study was designed according to the PRISMA-P guidelines. We will include case-control studies and cohort studies investigating the relationship between gene SNPs and depression and coronary heart disease comorbidities. The Newcastle-Ottawa Scale (NOS) will be used to assess the risk of bias. When measuring dichotomous outcomes, we will use the odds ratio (OR) and 95% confidence interval (95%CIs) in a case-control study. Five genetic models (allele model, homozygous model, co-dominant model, dominant model, and recessive model) will be evaluated for each included study. Subgroup analysis by ethnicity will be performed. If necessary, post hoc analysis will be made according to different types.
UNASSIGNED: A total of 13 studies were included in this study, and the types of genes included are FKBP5 and SGK1 genes that act on glucocorticoid; miR-146a, IL-4-589, IL-6-174, TNF-α-308, CRP-717 genes that act on inflammatory mechanisms; eNOS genes from endothelial cells; HSP70 genes that act on the autoimmune response; ACE2 and MAS1 genes that act to mediate Ang(1-7) in the RAS system; 5-HTTLPR gene responsible for the transport of serotonin 5-HT and neurotrophic factor BDNF gene. There were three studies on 5-HTTLPR and BDNF genes, respectively, while there was only one study targeting FKBP5, SGK1, miR-146a, IL-4-589, IL-6-174, TNF-alpha-308, CRP-717, eNOS, HSP70, ACE2, and MAS1 genes. We did not perform a meta-analysis for genes reported in a single study, and meta-analysis was performed separately for studies exploring the 5-HTTLPR and BDNF genes. The results showed that for the 5-HTTLPR gene, there was a statistically significant association between 5-HTTLPR gene polymorphisms and depression in combination with coronary diseases (CHD-D) under the co-dominant model (LS vs LL: OR 1.76, 95%CI 1.20-2.59; SS vs LL: OR 2.80, 95%CI 1.45 to 5.41), the dominant model (LS+SS vs LL: OR 2.06, 95%CI 1.44 to 2.96), and the homozygous model (SS vs LL: OR 2.80 95%CI 1.45 to 5.5.41) were statistically significant for CHD-D, demonstrating that polymorphisms in the 5-HTTLPR gene are associated with the development of CHD-D and that the S allele in the 5-HTTLPR gene is likely to be a risk factor for CHD-D. For the BDNF gene, there were no significant differences between one of the co-dominant gene models (AA vs GG: OR 6.63, 95%CI 1.44 to 30.64), the homozygous gene model (AA vs GG: OR 6.63,95% CI 1.44 to 30.64), the dominant gene model (GA+AA vs GG: OR4.29, 95%CI 1.05 to 17.45), recessive gene model (AA vs GG+GA: OR 2.71, 95%CI 1.16 to 6.31), and allele model (A vs G: OR 2.59, 95%CI 1.18 to 5.67) were statistically significant for CHD-D, demonstrating that BDNFrs6265 gene polymorphisms are associated with the CHD-D development and that the A allele in the BDNFrs6265 gene is likely to be a risk factor for CHD-D. We analyzed the allele frequencies of SNPs reported in a single study and found that the SNPs in the microRNA146a gene rs2910164, the SNPs in the ACE2 gene rs2285666 and the SNPs in the SGK1 gene rs1743963 and rs1763509 were risk factors for the development of CHD-D. We performed a subgroup analysis of three studies involving the BDNFrs6265 gene. The results showed that European populations were more at risk of developing CHD-D than Asian populations in both dominant model (GA+AA vs GG: OR 10.47, 95%CI 3.53 to 31.08) and co-dominant model (GA vs GG: OR 6.40, 95%CI 1.98 to 20.73), with statistically significant differences. In contrast, the studies involving the 5-HTTLPR gene were all Asian populations, so subgroup analyses were not performed. We performed sensitivity analyses of studies exploring the 5-HTTLPR and BDNF rs6265 genes. The results showed that the results of the allele model, the dominant model, the recessive model, the homozygous model and the co-dominant model for both 5-HTTLPR and BDNF rs6265 genes were stable. Due to the limited number of studies of the 5-HTTLPR and BDNF genes, it was not possible to determine the symmetry of the funnel plot using Begg\'s funnel plot and Egger\'s test. Therefore, we did not assess publication bias.
UNASSIGNED: SNPs of the microRNA146a gene at rs2910164, the ACE2 gene at the rs2285666 and the SGK1 gene at rs1743963 and rs1763509, and the SNPs at the 5-HTTLPR and BDNF gene loci are associated with the onset of comorbid depression in coronary heart disease. We recommend that future research focus on studying SNPs\' impact on comorbid depression in coronary heart disease, specifically targeting the 5-HTTLPR and BDNF gene at rs6265.
UNASSIGNED: https://www.crd.york.ac.uk/prospero/, identifier CRD42021229371.
UNASSIGNED: This study was designed according to the PRISMA-P guidelines. We will include case-control studies and cohort studies investigating the relationship between gene SNPs and depression and coronary heart disease comorbidities. The Newcastle-Ottawa Scale (NOS) will be used to assess the risk of bias. When measuring dichotomous outcomes, we will use the odds ratio (OR) and 95% confidence interval (95%CIs) in a case-control study. Five genetic models (allele model, homozygous model, co-dominant model, dominant model, and recessive model) will be evaluated for each included study. Subgroup analysis by ethnicity will be performed. If necessary, post hoc analysis will be made according to different types.
UNASSIGNED: A total of 13 studies were included in this study, and the types of genes included are FKBP5 and SGK1 genes that act on glucocorticoid; miR-146a, IL-4-589, IL-6-174, TNF-α-308, CRP-717 genes that act on inflammatory mechanisms; eNOS genes from endothelial cells; HSP70 genes that act on the autoimmune response; ACE2 and MAS1 genes that act to mediate Ang(1-7) in the RAS system; 5-HTTLPR gene responsible for the transport of serotonin 5-HT and neurotrophic factor BDNF gene. There were three studies on 5-HTTLPR and BDNF genes, respectively, while there was only one study targeting FKBP5, SGK1, miR-146a, IL-4-589, IL-6-174, TNF-alpha-308, CRP-717, eNOS, HSP70, ACE2, and MAS1 genes. We did not perform a meta-analysis for genes reported in a single study, and meta-analysis was performed separately for studies exploring the 5-HTTLPR and BDNF genes. The results showed that for the 5-HTTLPR gene, there was a statistically significant association between 5-HTTLPR gene polymorphisms and depression in combination with coronary diseases (CHD-D) under the co-dominant model (LS vs LL: OR 1.76, 95%CI 1.20-2.59; SS vs LL: OR 2.80, 95%CI 1.45 to 5.41), the dominant model (LS+SS vs LL: OR 2.06, 95%CI 1.44 to 2.96), and the homozygous model (SS vs LL: OR 2.80 95%CI 1.45 to 5.5.41) were statistically significant for CHD-D, demonstrating that polymorphisms in the 5-HTTLPR gene are associated with the development of CHD-D and that the S allele in the 5-HTTLPR gene is likely to be a risk factor for CHD-D. For the BDNF gene, there were no significant differences between one of the co-dominant gene models (AA vs GG: OR 6.63, 95%CI 1.44 to 30.64), the homozygous gene model (AA vs GG: OR 6.63,95% CI 1.44 to 30.64), the dominant gene model (GA+AA vs GG: OR4.29, 95%CI 1.05 to 17.45), recessive gene model (AA vs GG+GA: OR 2.71, 95%CI 1.16 to 6.31), and allele model (A vs G: OR 2.59, 95%CI 1.18 to 5.67) were statistically significant for CHD-D, demonstrating that BDNFrs6265 gene polymorphisms are associated with the CHD-D development and that the A allele in the BDNFrs6265 gene is likely to be a risk factor for CHD-D. We analyzed the allele frequencies of SNPs reported in a single study and found that the SNPs in the microRNA146a gene rs2910164, the SNPs in the ACE2 gene rs2285666 and the SNPs in the SGK1 gene rs1743963 and rs1763509 were risk factors for the development of CHD-D. We performed a subgroup analysis of three studies involving the BDNFrs6265 gene. The results showed that European populations were more at risk of developing CHD-D than Asian populations in both dominant model (GA+AA vs GG: OR 10.47, 95%CI 3.53 to 31.08) and co-dominant model (GA vs GG: OR 6.40, 95%CI 1.98 to 20.73), with statistically significant differences. In contrast, the studies involving the 5-HTTLPR gene were all Asian populations, so subgroup analyses were not performed. We performed sensitivity analyses of studies exploring the 5-HTTLPR and BDNF rs6265 genes. The results showed that the results of the allele model, the dominant model, the recessive model, the homozygous model and the co-dominant model for both 5-HTTLPR and BDNF rs6265 genes were stable. Due to the limited number of studies of the 5-HTTLPR and BDNF genes, it was not possible to determine the symmetry of the funnel plot using Begg\'s funnel plot and Egger\'s test. Therefore, we did not assess publication bias.
UNASSIGNED: SNPs of the microRNA146a gene at rs2910164, the ACE2 gene at the rs2285666 and the SGK1 gene at rs1743963 and rs1763509, and the SNPs at the 5-HTTLPR and BDNF gene loci are associated with the onset of comorbid depression in coronary heart disease. We recommend that future research focus on studying SNPs\' impact on comorbid depression in coronary heart disease, specifically targeting the 5-HTTLPR and BDNF gene at rs6265.
UNASSIGNED: https://www.crd.york.ac.uk/prospero/, identifier CRD42021229371.
摘要：
■抑郁症和冠心病（CHD）具有共同的风险机制。常见的单核苷酸多态性（SNP）可能与抑郁症合并冠心病的风险有关。
■本研究是根据PRISMA-P指南设计的。我们将包括病例对照研究和队列研究，调查基因SNP与抑郁症和冠心病合并症之间的关系。纽卡斯尔-渥太华量表（NOS）将用于评估偏倚的风险。当测量二分法的结果时，我们将在病例对照研究中使用比值比(OR)和95%置信区间(95CIs).五种遗传模型(等位基因模型，纯合模型，共同主导模型，主导模型，和隐性模型）将对每个纳入的研究进行评估。按种族进行亚组分析。如有必要,根据不同类型进行事后分析。
■本研究共纳入13项研究，包括的基因类型是作用于糖皮质激素的FKBP5和SGK1基因；miR-146a，作用于炎症机制的IL-4-589，IL-6-174，TNF-α-308，CRP-717基因；来自内皮细胞的eNOS基因；作用于自身免疫反应的HSP70基因；在RAS系统中介导Ang（1-7）的ACE2和MAS1基因；5-HTTLPR基因负责5-羟色胺5-HT和神经营养因子BDNF基因的转运。有三个关于5-HTTLPR和BDNF基因的研究，分别,虽然只有一项研究针对FKBP5，SGK1，miR-146a，IL-4-589,IL-6-174,TNF-α-308,CRP-717,eNOS,HSP70、ACE2和MAS1基因。我们没有对一项研究中报道的基因进行荟萃分析，并对探索5-HTTLPR和BDNF基因的研究分别进行荟萃分析。结果表明,对于5-HTTLPR基因,在共显性模型下，5-HTTLPR基因多态性与合并冠心病（CHD-D）的抑郁症之间存在统计学上的显着关联（LSvsLL：OR1.76，95CI1.20-2.59；SSvsLL：OR2.80，95CI1.45至5.41），主导模型(LS+SS与LL：OR2.06，95CI1.44至2.96)，纯合模型（SSvsLL：OR2.8095CI1.45至5.5.41）对CHD-D有统计学意义，证明5-HTTLPR基因的多态性与CHD-D的发展有关，并且5-HTTLPR基因中的S等位基因可能是CHD-D的危险因素。对于BDNF基因,共显性基因模型之一之间没有显着差异（AAvsGG：OR6.63，95CI1.44至30.64），纯合基因模型(AA与GG：OR6.63,95%CI1.44至30.64)，显性基因模型（GA+AAvsGG：OR4.29，95CI1.05至17.45），隐性基因模型（AA与GG+GA：OR2.71，95CI1.16至6.31），和等位基因模型（AvsG：OR2.59，95CI1.18至5.67）对CHD-D有统计学意义，证明BDNFrs6265基因多态性与CHD-D的发展有关，并且BDNFrs6265基因中的A等位基因可能是CHD-D的危险因素。我们分析了一项研究中报道的SNP的等位基因频率，发现microRNA146a基因rs2910164中的SNP，ACE2基因rs2285666中的SNP以及SGK1基因rs1743963和rs1763509中的SNP是CHD-D发展的危险因素。我们对涉及BDNFrs6265基因的三项研究进行了亚组分析。结果表明，在显性模型（GAAAvsGG：OR10.47，95CI3.53至31.08）和共显性模型（GAvsGG：OR6.40，95CI1.98至20.73）中，欧洲人群比亚洲人群更容易患CHD-D。具有统计学上的显著差异。相比之下,涉及5-HTTLPR基因的研究都是亚洲人群，因此未进行亚组分析.我们对探索5-HTTLPR和BDNFrs6265基因的研究进行了敏感性分析。结果表明,等位基因模型的结果,主导模式，隐性模型，5-HTTLPR和BDNFrs6265基因的纯合模型和共显性模型是稳定的。由于对5-HTTLPR和BDNF基因的研究数量有限，使用Begg的漏斗图和Egger的测试无法确定漏斗图的对称性。因此,我们没有评估发表偏倚.
■rs2910164处的microRNA146a基因，rs2285666处的ACE2基因和rs1743963和rs1763509处的SGK1基因的SNP，以及5-HTTLPR和BDNF基因位点的SNP与冠心病并发抑郁症的发作有关。我们建议未来的研究重点是研究SNP对冠心病合并抑郁的影响。特异性靶向rs6265的5-HTTLPR和BDNF基因。
■https://www.crd.约克。AC.英国/普华永道/，标识符CRD42021229371。
■本研究是根据PRISMA-P指南设计的。我们将包括病例对照研究和队列研究，调查基因SNP与抑郁症和冠心病合并症之间的关系。纽卡斯尔-渥太华量表（NOS）将用于评估偏倚的风险。当测量二分法的结果时，我们将在病例对照研究中使用比值比(OR)和95%置信区间(95CIs).五种遗传模型(等位基因模型，纯合模型，共同主导模型，主导模型，和隐性模型）将对每个纳入的研究进行评估。按种族进行亚组分析。如有必要,根据不同类型进行事后分析。
■本研究共纳入13项研究，包括的基因类型是作用于糖皮质激素的FKBP5和SGK1基因；miR-146a，作用于炎症机制的IL-4-589，IL-6-174，TNF-α-308，CRP-717基因；来自内皮细胞的eNOS基因；作用于自身免疫反应的HSP70基因；在RAS系统中介导Ang（1-7）的ACE2和MAS1基因；5-HTTLPR基因负责5-羟色胺5-HT和神经营养因子BDNF基因的转运。有三个关于5-HTTLPR和BDNF基因的研究，分别,虽然只有一项研究针对FKBP5，SGK1，miR-146a，IL-4-589,IL-6-174,TNF-α-308,CRP-717,eNOS,HSP70、ACE2和MAS1基因。我们没有对一项研究中报道的基因进行荟萃分析，并对探索5-HTTLPR和BDNF基因的研究分别进行荟萃分析。结果表明,对于5-HTTLPR基因,在共显性模型下，5-HTTLPR基因多态性与合并冠心病（CHD-D）的抑郁症之间存在统计学上的显着关联（LSvsLL：OR1.76，95CI1.20-2.59；SSvsLL：OR2.80，95CI1.45至5.41），主导模型(LS+SS与LL：OR2.06，95CI1.44至2.96)，纯合模型（SSvsLL：OR2.8095CI1.45至5.5.41）对CHD-D有统计学意义，证明5-HTTLPR基因的多态性与CHD-D的发展有关，并且5-HTTLPR基因中的S等位基因可能是CHD-D的危险因素。对于BDNF基因,共显性基因模型之一之间没有显着差异（AAvsGG：OR6.63，95CI1.44至30.64），纯合基因模型(AA与GG：OR6.63,95%CI1.44至30.64)，显性基因模型（GA+AAvsGG：OR4.29，95CI1.05至17.45），隐性基因模型（AA与GG+GA：OR2.71，95CI1.16至6.31），和等位基因模型（AvsG：OR2.59，95CI1.18至5.67）对CHD-D有统计学意义，证明BDNFrs6265基因多态性与CHD-D的发展有关，并且BDNFrs6265基因中的A等位基因可能是CHD-D的危险因素。我们分析了一项研究中报道的SNP的等位基因频率，发现microRNA146a基因rs2910164中的SNP，ACE2基因rs2285666中的SNP以及SGK1基因rs1743963和rs1763509中的SNP是CHD-D发展的危险因素。我们对涉及BDNFrs6265基因的三项研究进行了亚组分析。结果表明，在显性模型（GAAAvsGG：OR10.47，95CI3.53至31.08）和共显性模型（GAvsGG：OR6.40，95CI1.98至20.73）中，欧洲人群比亚洲人群更容易患CHD-D。具有统计学上的显著差异。相比之下,涉及5-HTTLPR基因的研究都是亚洲人群，因此未进行亚组分析.我们对探索5-HTTLPR和BDNFrs6265基因的研究进行了敏感性分析。结果表明,等位基因模型的结果,主导模式，隐性模型，5-HTTLPR和BDNFrs6265基因的纯合模型和共显性模型是稳定的。由于对5-HTTLPR和BDNF基因的研究数量有限，使用Begg的漏斗图和Egger的测试无法确定漏斗图的对称性。因此,我们没有评估发表偏倚.
■rs2910164处的microRNA146a基因，rs2285666处的ACE2基因和rs1743963和rs1763509处的SGK1基因的SNP，以及5-HTTLPR和BDNF基因位点的SNP与冠心病并发抑郁症的发作有关。我们建议未来的研究重点是研究SNP对冠心病合并抑郁的影响。特异性靶向rs6265的5-HTTLPR和BDNF基因。
■https://www.crd.约克。AC.英国/普华永道/，标识符CRD42021229371。
