Introduction
Methods
Search strategy and eligible study selection criteria
Data extraction
Methodological quality
Statistical analysis
Criteria of consideration | Category | Proposed operationalization |
---|---|---|
Amount of evidence | A | Sample size over 1000 |
B | Sample size 100–1000 | |
C | Sample size under 100 | |
Replication | A | I2 < 50% |
B | 25% < I2 < 50% | |
C | I2 > 50% | |
Protection from bias | A | Consideration biases such as bias in genotyping, population stratification, and Selective reporting biases |
B | Bias in genotype definition = Not reported what was done/No quality control checks/Appropriate quality control checks | |
C | Population stratification = Not reported what was done/Nothing done/Same descent group/Adjustment for reported descent/Family-based design/Genomic control, PCA or similar method Selective reporting biases = Meta-analysis of published data/Retrospective efforts to include unpublished data/Meta-analysis within consortium |
Results
Number of articles and type identified
Main findings of the meta-analyses of SNP-based studies
Genetic variant | Gene (or near gene) | Reference (year of data collection) | Ethnicity | Sample size (case/control) | Included studies | Minor allele & Reference allele | Genetic model | Type of model | Reported OR (95% CI) | p value for genetic main effect | Heterogeneity (%) | Venice criteria | Evidence class |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
rs2012390 | MMP-8 | Jiang et al. [30] | Asian | 884/1012 | 3 | A & G | Allele model | Fixed effect | 1.34 [1.00–1.79] | 0.005 | 0 | NA | NA |
Heterozygote model | Fixed effect | 1.40 [1.14–1.73] | 0.002 | 0 | NA | NA | |||||||
Dominant model | Fixed effect | 1.39 [1.13–1.71] | 0.002 | 0 | NA | NA | |||||||
rs11225394 | MMP-8 | Jiang et al. [30] | Asian | 1184/1211 | 3 | C & T | Heterozygote model | Fixed effect | 0.63 [0.51–0.77] | < 0.00001 | 21 | AAB (equivalent to AAA) | Strong |
rs1800629 | TNF-α | Peng et al. [31] | Caucasian/Asian | 432/760 | 7 | G & A | Allele model | Fixed effect | 0.73 [0.57–0.93] | 0.012 | 17.50 | NA | NA |
Homozygote model | Fixed effect | 0.52 [0.26–1.05] | 0.069 | 10.00 | NA | NA | |||||||
Heterozygote model | Fixed effect | 0.68 | 0.324 | 6.60 | NA | NA | |||||||
Dominant model | Fixed effect | 0.54 [0.27–1.09] | 0.085 | 10.40 | NA | NA | |||||||
Recessive model | Fixed effect | 0.73 [0.54–0.97] | 0.029 | 0 | NA | NA | |||||||
rs361525 | TNF-α | Peng et al. [31] | Caucasian/Asian | 432/760 | 3 | G & A | Allele model | Fixed effect | 0.27 [0.15–0.49] | < 0.001 | 0 | AAB (equivalent to AAA) | Strong |
Recessive model | Fixed effect | 0.25 [0.14–0.47] | < 0.001 | 0 | AAB (equivalent to AAA) | Strong | |||||||
VNTR in intron 4 | eNOS | Song and Lee [32] | Caucasian/Asian | 296/329 | 3 | 4a & 4b | Allele model | Fixed effect | 3.24 [2.04–5.15] | < 0.001 | 0 | BAB | Moderate |
Dominant model | Fixed effect | 3.50 [2.12–5.78] | < 0.001 | 0 | BAB | Moderate | |||||||
193/226 | 2 | 4a & 4b | Recessive model | Fixed effect | 4.76 [0.77–59.61] | 0.094 | 0 | NA | NA | ||||
rs1799983 | eNOS | Song and Lee [32] | Asian | 403/661 | 3 | T & G | Allele model | Random effect | 1.72 [0.80–3.70] | 0.006 | 80.20 | ABB | Moderate |
rs2070744 | eNOS | Song and Lee [32] | Asian/NA | 145/378 | 2 | C & T | Allele model | Random effect | 1.03 [0.19–5.96] | 0.001 | 90 | ABB | Moderate |
rs2010963 | VEGF | Hong et al. [33] | Asian | 697/877 | 3 | C & G | Homozygote model | Fixed effect | 0.82 [0.72–0.93] | 0.002 | 0 | AAB (equivalent to AAA) | Strong |
Dominant model | Fixed effect | 0.79 [0.67–0.92] | 0.003 | 0 | AAB (equivalent to AAA) | Strong | |||||||
Recessive model | Fixed effect | 1.29 [1.06–1.59] | 0.015 | 0 | NA | NA | |||||||
rs6025 | Factor V | Shang et al. [34] | Mixed | 481/867 | 7 | A & G | Homozygote model | Fixed effect | 4.55 [2.75–7.52] | < 0.001 | 0 | AAB (equivalent to AAA) | Strong |
Genetic variant | Gene (or near gene) | Reference (year of data collection) | Ethnicity | Sample size (case/control) | Included studies | Minor allele & major allele | Genetic model | Type of model | Reported OR (95% CI) | p value for genetic main effect | Heterogeneity (%) | Venice criteria | Evidence class |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
rs693 | ApoB | Chen et al. [35] | Mixed | 570 (total) | 4 | C & T | Allelic model | NA | 2.63 [0.92–7.53] | 0.072 | 58.00 | NA | NA |
Heterozygous model | NA | 2.46 [1.27–4.77] | 0.008 | 54.50 | NA | NA | |||||||
Homozygous model | NA | 7.70 [1.23–48.18] | 0.029 | 24.40 | NA | NA | |||||||
Recessive model | NA | 7.16 [1.19–43.05] | 0.031 | 32.10 | NA | NA | |||||||
rs693 | ApoB | Chen et al. [35] | Mixed | 725 (total) | 5 | C & T | Dominant model | NA | 2.99 [1.71–5.22] | < 0.001 | 31.30 | BBB | Moderate |
rs1042031 | ApoB | Chen et al. [35] | Mixed | 572 (total) | 4 | G & A/C | Dominant model | NA | 2.90 [1.49–5.65] | 0.002 | 50.30 | BCB | Weak |
rs1042031 | ApoB | Chen et al. [35] | China | 415 (total) | 3 | G & A/C | Dominant model | NA | 4.81 [2.05–11.30] | < 0.001 | 0 | BAB | Moderate |
rs1801133 | MTHFR | Chen et al. [35] | Mixed | 251 (total) | 3 | C & T | Allelic | NA | 0.92 [0.59–1.44] | 0.710 | 12.90 | NA | NA |
Heterozygous model | NA | 0.62 [0.33–1.17] | 0.144 | 22.10 | NA | NA | |||||||
Homozygous model | NA | 1.24 [0.48–3.21] | 0.653 | 0 | NA | NA | |||||||
Recessive model | NA | 1.54 [0.63–3.76] | 0.339 | 0 | NA | NA | |||||||
507 (total) | 4 | C & T | Dominant model | NA | 0.94 [0.61–1.45] | 0.775 | 23.40 | NA | NA | ||||
rs1045642 | ABCB1 | Zhou et al. [36] | Asian/mixed | 336/712 | 7 | T & C | Allelic | Fixed effect | 0.68 [0.54–0.84] | 0.295 | 18.30 | NA | NA |
Heterozygous model | Fixed effect | 0.73 [0.53–1.00] | 0.722 | 0 | NA | NA | |||||||
Homozygote model | Random effect | 0.43 [0.26–0.69] | 0.049 | 58.10 | NA | NA | |||||||
Recessive model | Random effect | 0.52 [0.34–0.81] | 0.009 | 70.30 | NA | NA | |||||||
Dominant model | Fixed effect | 0.64 [0.48–0.87] | 0.830 | 0 | NA | NA | |||||||
rs2032582 | ABCB1 | Zhou et al. [36] | Mixed | 275/574 | 5 | T/A &G | Allelic | Fixed effect | 0.73 [0.58–0.90] | 0.587 | 0 | NA | NA |
Heterozygous model | Fixed effect | 0.66 [0.45–0.96] | 0.985 | 0 | NA | NA | |||||||
Homozygote model | Fixed effect | 0.52 [0.34–0.82] | 0.560 | 0 | NA | NA | |||||||
Recessive model | Fixed effect | 0.71 [0.49–1.01] | 0.385 | 3.9 | NA | NA | |||||||
Dominant model | Fixed effect | 0.61 [0.43–0.87] | 0.959 | 0 | NA | NA | |||||||
rs1799889 | PAI-1 | Gong et al. [37] | Mixed | 108/917 | 4 | 4G/5G | Allele model | NA | 1.93 [1.15–3.26] | 0.014 | 0.0004 (P) | NA | NA |
Homozygote model | NA | 3.22 [1.67–6.21] | < 0.0005 | 0.00111 (P) | ACB | Moderate | |||||||
Dominant model | NA | 2.31 [1.53–3.49] | < 0.0005 | 0.06 (P) | ACB | Moderate | |||||||
Recessive model | NA | 2.30 [1.24–4.30] | 0.009 | 0.162 (P) | NA | NA |
Qualitative methodological appraisal of eligible meta-analyses
References | Checklist | Total | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | ||
Chen et al. [35] | 1 | 0.5 | 1 | 0.5 | 1 | 1 | 0 | 0.5 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 9.5 |
Jiang et al. [30] | 1 | 0.5 | 1 | 0.5 | 1 | 1 | 0 | 0.5 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 8.5 |
Peng et al. [31] | 1 | 0.5 | 1 | 0.5 | 1 | 1 | 0 | 0.5 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 9.5 |
Song et al., [32] | 1 | 0.5 | 1 | 0 | 0 | 0 | 0 | 0.5 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 7 |
Hong et al. [33] | 1 | 0.5 | 1 | 0.5 | 1 | 1 | 0 | 0.5 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 9.5 |
Zhou et al. [36] | 1 | 0.5 | 1 | 0 | 1 | 1 | 0 | 0.5 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 9 |
Shang et al. [34] | 1 | 0.5 | 1 | 0.5 | 1 | 1 | 0 | 0.5 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 7.5 |
Gong et al. [37] | 1 | 0.5 | 1 | 0.5 | 1 | 1 | 0 | 0.5 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 8.5 |