Increased frequency of angiotensin converting enzyme D allele in Chinese Han patients with idiopathic pulmonary fibrosis: A systematic review and meta-analysis

Figures

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  Figure 1.. PRISMA literature screening flow chart (161 relevant literatures were initially found in the 5 databases and after tiered screening, 4 studies were finally included).

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  Figure 2.. The association between ACE gene I/D polymorphism and IPF susceptibility was evaluated by allele genetic model (D vs I). (A) Forest plot of D versus I genetic model (The D allele was correlated with the risk of IPF in the Chinese Han population [OR] = 0.53, 95% CI [0.42, 0.67], P < .00001). (B) Trial sequential analysis (Adjusted Boundaries Print) of ACE I/D polymorphism and IPF risk using the D versus I genetic model. The calculated Required information size (RIS) was 6429, and the cumulative Z curve crossed the conventional boundary and the Trial sequential monitoring (TSA) boundary. The Blue line was cumulative Z curve; The Red line was the TSA boundary or RIS. The Green line was the Conventional boundary. (C) Influence analysis results of D versus I (The minimum of all the research results was not lower than the number 1). (D) Inverted funnel plot of D versus I (The inverted funnel plot showed symmetry, indicating that there was no obvious bias). 95% CI = 95% confidence interval, ACE = angiotensin converting enzyme, I/D = insert/defect, IPF = idiopathic pulmonary fibrosis, OR = odds ratio.

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  Figure 3.. The association between ACE gene I/D polymorphism and IPF susceptibility was evaluated by dominant genetic model (DD + ID vs II). (A) Forest plot of DD + ID versus II genetic model. The DD + ID genotype was not correlated with the risk of IPF (OR = 0.73, 95% CI [0.52, 1.05], P = .09). (B) Trial sequential analysis (Adjusted Boundaries Print) of ACE I/D polymorphism and IPF risk using the DD + ID versus II genetic model. The calculated RIS was 6670 and the cumulative Z curve crossed the conventional boundary. The Blue line is cumulative Z curve; The Red line is the Trial sequential monitoring (TSA) boundary or Required information size (RIS); The Green line is the Conventional boundary. 95% CI = 95% confidence interval, ACE = angiotensin converting enzyme, I/D = insert/defect, IPF = idiopathic pulmonary fibrosis, OR = odds ratio.

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  Figure 4.. The association between ACE gene I/D polymorphism and IPF susceptibility was evaluated by recessive genetic model (DD vs II + ID). (A) Forest plot of DD versus II + ID genetic model. The DD genotype was correlated with the risk of IPF (OR = 0.30, 95% CI [0.21, 0.43], P < .00001). (B) Trial sequential analysis (Adjusted Boundaries Print) of ACE I/D polymorphism and IPF risk using the DD versus II + ID genetic model. The calculated RIS was 6429 and the cumulative Z curve crossed the conventional boundary. The Blue line is cumulative Z curve; The Red line is the Trial sequential monitoring (TSA) boundary or Required information size (RIS); The Green line is the Conventional boundary). 95% CI = 95% confidence interval, ACE = angiotensin converting enzyme, I/D = insert/defect, IPF = idiopathic pulmonary fibrosis, OR = odds ratio.

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  Figure 5.. The association between ACE gene I/D polymorphism and IPF susceptibility was evaluated by additive genetic model (DD vs II). (A) Forest plot of DD versus II genetic model. The DD genotype was correlated with the risk of IPF (OR = 0.37, 95% CI [0.24, 0.57], P < .00001). (B) Trial sequential analysis (Adjusted Boundaries Print) of ACE I/D polymorphism and IPF risk using the DD versus II genetic model. The calculated RIS was 6429 and the cumulative Z curve crossed the conventional boundary. The Blue line is cumulative Z curve; The Red line is the Trial sequential monitoring (TSA) boundary or Required information size (RIS); The Green line is the Conventional boundary. 95% CI = 95% confidence interval, ACE = angiotensin converting enzyme, I/D = insert/defect, IPF = idiopathic pulmonary fibrosis, OR = odds ratio.

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  Figure 6.. The association between ACE gene I/D polymorphism and IPF susceptibility was evaluated by heterozygous genetic model (ID vs II). (A) Forest plot of ID versus II genetic model. There was no correlation between ID genotype and the risk of IPF (OR = 1.25, 95% CI [0.71, 2.22], P = .44). (B) Trial sequential analysis (Adjusted Boundaries Print) of ACE I/D polymorphism and IPF risk using the ID versus II genetic model. The calculated RIS is 7449. The combined sample size did not exceed the RIS, and the cumulative Z curve did not cross the conventional boundary and the TSA boundary. The Blue line is cumulative Z curve; The Red line is the Trial sequential monitoring (TSA) boundary or Required information size (RIS); The Green line is the Conventional boundary. 95% CI = 95% confidence interval, ACE = angiotensin converting enzyme, I/D = insert/defect, IPF = idiopathic pulmonary fibrosis, OR = odds ratio.

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  Figure 7.. Forest plot of Ang Ⅱ changes. The level of Ang Ⅱ in IPF group was higher than that in control group (MD = 14.29, 95% CI [11.20, 17.37], P < .00001). 95% CI = 95% confidence interval, Ang II = angiotensin II, IPF = idiopathic pulmonary fibrosis, MD = mean difference.