Background
Materials and methods
Literature search
Study selection
Data extraction
Quality assessment
Statistical analysis
Results
Overall characteristics of selected studies and quality assessment
Refs | Year | Country | Ethnicity | Case/Control | Mean age of AMD | Mean age of control | Typing teaching | Study design |
---|---|---|---|---|---|---|---|---|
Yate et al. [54] | 2007 | UK | Caucasian | 603/350 | 79.4 ± 7.2 | 75.3 ± 7.8 | SNaPshot | Sex-,age-,ethnic-,matched |
Yate et al. [54] | 2007 | Scotland | Caucasian | 244/351 | 77.8 ± 9.2 | 78.0 ± 8.5 | TaqMan | Sex-,age-,ethnic-,matched |
Maller et al. [41] | 2007 | America | Caucasian | 1238/934 | NA | NA | MALDI-TOF MS | Age-,ethnic-, matched |
Edwards et al. [31] | 2008 | America | Caucasian | 444/300 | NA | NA | Illumina GoldenGate | Age-,ethnic-, matched |
Spencer et al. [50] | 2008 | America | Caucasian | 286/701 | 76.5 ± 7.7 | 66.9 ± 8.3 | TaqMan | Sex-,age-,ethnic-,matched |
Scholl et al. [4] | 2009 | German | Caucasian | 99/612 | 71.8 ± 7.4 | 76.2 ± 5.3 | MALDI-TOF MS | Sex-,age-,ethnic-,matched |
Francis et al. [32] | 2009 | America | Caucasian | 211/187 | 79 | 74 | Sequencing | Age-,ethnic-, matched |
Park et al. [44] | 2009 | America | Caucasian | 898/599 | 80.6 ± 5.0 | 77.6 ± 4.3 | Illumina GoldenGate | Sex-,age-,ethnic-,matched |
Despriet et al. [30] | 2009 | Netherlands | Caucasian | 268/173 | 78.7 ± 7.7 | 74.1 ± 6.3 | TaqMan | Sex-,age-,ethnic-,matched |
Bergeron et al. [22] | 2009 | America | Caucasian | 421/215 | 64.8 | 66.5 | TaqMan | Sex-,age-,ethnic-,matched |
Reynolds et al. [47] | 2009 | America | Caucasian | 120/60 | 82.0 ± 6.9 | 79.0 ± 4.4 | MALDI-TOF MS | Sex-,age-,ethnic-,matched |
Pei et al.[45] | 2009 | China | East Asian | 123/130 | 70.6 ± 8.2 | 69.2 ± 10.1 | MALDI-TOF MS | Sex-,age-,ethnic-, matched |
Cui et al. [29] | 2010 | China | East Asian | 150/161 | 66.6 ± 8.4 | 65.7 ± 7.8 | PCR-RFLP/ Sequencing | Sex-,age-,ethnic-, matched |
Zerbib et al. [56] | 2010 | France | Caucasian | 1080/406 | 79.0 ± 7.4 | 67.8 ± 7.7 | TaqMan | Sex-,age-,ethnic-, matched |
McKay et al. [43] | 2010 | Northern Ireland | Caucasian | 437/436 | 77.6 | 74.9 | SNaPshot | Sex-,age-,ethnic-, matched |
Chen et al. [25] | 2010 | America | Caucasian | 2157/1150 | 78.6 | 74.1 | Illumina GoldenGate | Sex-,age-,ethnic-, matched |
Kopplin et al. [37] | 2010 | America | Caucasian | 377/161 | NA | NA | Affymetrix GeneChip | Age-,ethnic-, matched |
Liu et al. [39] | 2010 | China | East Asian | 158/220 | 64.0 ± 6.6 | 63.0 ± 7.8 | SNaPshot | Sex-,age-,ethnic-, matched |
Yu et al. [55] | 2011 | America | Caucasian | 1082/221 | 79.5 ± 5.5 | 77.0 ± 4.6 | MALDI-TOF MS | Sex-,age-,ethnic-, matched |
Chen et al. [26] | 2011 | America | Caucasian | 1335/509 | 70.2 ± 5.1 | 67.0 ± 4.3 | SNaPshot | Sex-,age-,ethnic-, matched |
Hageman et al. [33] | 2011 | America | Caucasian | 1132/822 | 76.5 ± 7.1 | 76.4 ± 7.3 | NA | Sex-,age-,ethnic-, matched |
Peter et al. [46] | 2011 | America | Caucasian | 48/1260 | NA | NA | TaqMan | Age-,ethnic-, matched |
Yanagisawa et al. [53] | 2011 | Japan | East Asian | 420/197 | 74.0 ± 7.5 | 72.0 ± 6.0 | TaqMan | Sex-,age-,ethnic-, matched |
Martinez et al. [42] | 2012 | Spain | Caucasian | 259/191 | NA | NA | SNaPshot | Age-,ethnic-, matched |
Smailhodzic et al. [49] | 2012 | Netherlands | Caucasian | 197/150 | NA | NA | Sequencing | Sex-,age-,ethnic-, matched |
Buentello et al. [23] | 2012 | Mexico | Caucasian | 159/152 | 76.4 ± 8.1 | 73.5 ± 6.8 | PCR-RFLP | Sex-,age-,ethnic-, matched |
Tian et al. [51] | 2012 | China | East Asian | 535/469 | NA | NA | MALDI-TOF MS | Age-,ethnic-, matched |
Losonczy et al. [40] | 2012 | Hungary | Caucasian | 275/106 | 76.0 ± 7.3 | 79.1 ± 6.1 | PCR-RFLP | Sex-,age-,ethnic-, matched |
Cipriani et al. [27] | 2012 | UK | Caucasian | 893/2199 | 78.6 ± 7.5 | NA | Illumina BeadChip | Sex-,age-,ethnic-, matched |
Jaouni et al. [36] | 2012 | Israel | Middle East | 317/159 | 78.1 ± 7.6 | 70.8 ± 8.2 | PCR-RFLP | Sex-,age-,ethnic-, matched |
Wu et al. [52] | 2013 | China | East Asian | 165/216 | 69.4 ± 10 | 64.5 ± 8.0 | TaqMan | Sex-,age-,ethnic-, matched |
Helgason et al. [35] | 2013 | Iceland | Caucasian | 1107/2869 | NA | NA | Illumina BeadChip | Age-,ethnic-, matched |
Helgason et al. [35] | 2013 | America | Caucasian | 1525/1288 | NA | NA | Illumina BeadChip | Age-,ethnic-, matched |
Contreras et al. [28] | 2014 | Mexico | Caucasian | 273/201 | 76.0 ± 8.0 | 65.5 ± 9.8 | TaqMan | Sex-,age-,ethnic-, matched |
Caire et al. [24] | 2014 | Spain | Caucasian | 154/141 | 75.4 ± 7.2 | 78.5 ± 7.2 | SNaPshot | Sex-,age-,ethnic-, matched |
Liu et al. [38] | 2014 | China | East Asian | 200/275 | 75.3 ± 7.7 | 74.3 ± 7.6 | TaqMan | Sex-,age-,ethnic-, matched |
Hautamaki et al. [34] | 2015 | Finland | Caucasian | 301/119 | NA | NA | Sequencing | Age-,ethnic-, matched |
Saksens et al. [48] | 2016 | Netherlands | Caucasian | 571/900 | 76.6 ± 8.5 | 71.3 ± 6.7 | KASP | Sex-,age-,ethnic-, matched |
2017 | Iran | Middle East | 266/228 | 76.4 ± 7.6 | 72.7 ± 6.8 | PCR-RFLP | Sex-,age-,ethnic-, matched | |
Habibi et al. [57] | 2017 | Tunisia | Middle East | 145/207 | 73.1 ± 8.1 | NA | PCR-SSP | Age-,ethnic-, matched |
Bias assessment of the included studies
Year | First author | Bias in selection of cases | Bias in selection of controls | Bias in genotyping controls | Bias in population stratification | Confounding bias | Multiple test and Selective outcome reports |
---|---|---|---|---|---|---|---|
2007 | Yate et al. [54] | NO | NO | NO | NO | NO | NO |
2007 | Maller et al. [41] | NO | NO | NO | NO | NO | NO |
2008 | Edwards et al. [31] | NO | NO | NO | NO | NO | NO |
2008 | Spencer et al. [50] | NO | NO | NO | NO | NO | NO |
2009 | Scholl et al. [4] | NO | NO | NO | NO | NO | NO |
2009 | Francis et al. [32] | NO | NO | NO | NO | NO | NO |
2009 | Park et al. [44] | NO | NO | NO | NO | NO | NO |
2009 | Despriet et al. [30] | NO | NO | NO | NO | NO | NO |
2009 | Bergeron et al. [22] | NO | NO | NO | NO | NO | NO |
2009 | Reynolds et al. [47] | NO | NO | NO | NO | NO | NO |
2009 | Pei et al. [45] | NO | NO | NO | NO | NO | NO |
2010 | Cui et al. [29] | NO | NO | NO | NO | NO | NO |
2010 | Zerbib et al. [56] | NO | NO | NO | NO | NO | NO |
2010 | McKay et al. [43] | NO | NO | NO | NO | NO | NO |
2010 | Chen et al. [25] | NO | NO | NO | NO | NO | NO |
2010 | Kopplin et al. [37] | NO | NO | NO | Unclear | NO | NO |
2010 | Liu et al. [39] | NO | NO | NO | NO | NO | NO |
2011 | Yu et al. [55] | NO | NO | NO | NO | NO | NO |
2011 | Chen et al. [26] | NO | NO | NO | NO | NO | NO |
2011 | Hageman et al. [33] | NO | NO | NO | Unclear | NO | NO |
2011 | Peter et al. [46] | Yes | NO | NO | Unclear | NO | NO |
2011 | Yanagisawa et al. [53] | NO | NO | NO | NO | NO | NO |
2012 | Martinez et al. [42] | NO | NO | NO | NO | NO | NO |
2012 | Smailhodzic et al. [49] | NO | NO | NO | NO | NO | NO |
2012 | Buentello et al. [23] | NO | NO | NO | NO | NO | NO |
2012 | Tian et al. [51] | NO | NO | NO | NO | NO | NO |
2012 | Losonczy et al. [40] | NO | NO | NO | NO | NO | NO |
2012 | Cipriani et al. [27] | NO | Yes | NO | NO | NO | NO |
2012 | Jaouni et al. [36] | NO | NO | NO | NO | NO | NO |
2013 | Wu et al. [52] | NO | NO | NO | NO | NO | NO |
2013 | Helgason et al. [35] | NO | NO | NO | NO | NO | NO |
2014 | Contreras et al. [28] | NO | NO | NO | NO | NO | NO |
2014 | Caire et al. [24] | NO | NO | NO | NO | NO | NO |
2014 | Liu et al. [38] | NO | NO | NO | NO | NO | NO |
2015 | Hautamaki et al. [34] | NO | NO | NO | NO | NO | NO |
2016 | Saksens et al. [48] | NO | NO | NO | NO | NO | NO |
2017 | NO | NO | NO | NO | NO | NO | |
2017 | Habibi et al. [57] | NO | NO | NO | NO | NO | NO |
Relationship of C3 gene polymorphisms with advanced AMD susceptibility
Subgroup | No. of studies | No. of patients | Allele model | Homozygote model | Heterozygote model | Dominant model | Recessive model | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Cases | Control | OR(95% CI) | P | OR(95% CI) | P | OR(95% CI) | P | OR(95% CI) | P | OR(95% CI) | P | ||
C3 rs2230199 (Associated allele vs. Reference allele: G vs. C) | |||||||||||||
Overall | 36 | 34,805 | 29,499 | 1.49 (1.39,1.59) | < 0.001 | 2.33 (1.98,2.74) | < 0.001 | 1.53 (1.41,1.64) | < 0.001 | 1.62 (1.51,1.74) | < 0.001 | 1.99 (1.70,2.34) | < 0.001 |
Caucasian | 28 | 31,372 | 26,130 | 1.48 (1.38,1.59) | < 0.001 | 2.20 (1.87,2.60) | < 0.001 | 1.55 (1.43,1.67) | < 0.001 | 1.63 (1.51,1.75) | < 0.001 | 1.88 (1.59,2.21) | < 0.001 |
East Asian | 5 | 2122 | 2388 | 1.11 (0.56,2.20) | 0.76 | – | – | 1.32 (0.91,1.93) | 0.144 | 1.49 (1.04,2.15) | 0.032 | 5.60 (1.57,19.9) | – |
Middle East | 3 | 1311 | 981 | 1.62 (1.33,1.97) | < 0.001 | – | – | 1.07 (0.66,1.73) | 0.798 | 1.49 (0.95,2.34) | 0.085 | 25.5 (3.35,194) | – |
C3 rs1047286 (Associated allele vs. Reference allele: T vs. C) | |||||||||||||
Overall | 13 | 16,232 | 16,222 | 1.45 (1.37,1.54) | < 0.001 | 2.06 (1.56,2.72) | < 0.001 | 1.72 (1.51,1.96) | < 0.001 | 1.76 (1.56,2.00) | < 0.001 | 1.71 (1.30,2.24) | < 0.001 |
Caucasian | 10 | 14,688 | 14,548 | 1.45 (1.37,1.54) | < 0.001 | 2.06 (1.56,2.72) | < 0.001 | 1.72 (1.50,1.96) | < 0.001 | 1.76 (1.55,2.00) | < 0.001 | 1.71 (1.30,2.24) | < 0.001 |
East Asian | 3 | 1544 | 1674 | 1.75 (0.49,6.29) | 0.388 | – | – | 2.06 (0.38,11.3) | 0.404 | 2.06 (0.38,11.3) | 0.404 | – | – |
C3 rs2230205 (Associated allele vs. Reference allele: A vs. G) | |||||||||||||
Overall | 5 | 3302 | 2732 | 0.99 (0.89,1.11) | 0.903 | 1.04 (0.77,1.42) | 0.780 | 1.00 (0.80,1.23) | 0.967 | 1.00 (0.81,1.22) | 0.992 | 1.06 (0.81,1.37) | 0.687 |
Caucasian | 1 | 880 | 598 | 0.90 (0.66,1.23) | 0.507 | 0.45 (0.12,1.60) | 0.215 | 0.98 (0.69,1.39) | 0.902 | 0.93 (0.66,1.32) | 0.699 | 0.45 (0.13,1.60) | 0.217 |
East Asian | 4 | 2422 | 2134 | 1.01 (0.89,1.14) | 0.903 | 1.10 (0.80,1.51) | 0.546 | 1.01 (0.77,1.32) | 0.967 | 1.04 (0.80,1.33) | 0.787 | 1.10 (0.84,1.43) | 0.497 |
C3 rs2250656 (Associated allele vs. Reference allele: G vs. A) | |||||||||||||
Overall | 5 | 3278 | 2632 | 0.90 (0.75,1.08) | 0.257 | 0.76 (0.49,1.16) | 0.207 | 0.78 (0.65,0.95) | 0.014 | 0.78 (0.65,0.94) | 0.010 | 0.83 (0.55,1.27) | 0.391 |
Caucasian | 1 | 874 | 512 | 0.82 (0.64,1.05) | 0.117 | 0.77 (0.42,1.42) | 0.407 | 0.76 (0.55,1.05) | 0.097 | 0.76 (0.56,1.04) | 0.085 | 0.87 (0.48,1.57) | 0.642 |
East Asian | 4 | 2404 | 2120 | 0.92 (0.73,1.16) | 0.486 | 0.74 (0.41,1.37) | 0.340 | 0.80 (0.63,1.02) | 0.068 | 0.79 (0.63,1.00) | 0.052 | 0.80 (0.44,1.45) | 0.456 |
Association between SNP rs2230199 of C3 gene and advanced AMD
Association between SNP rs1047286 of C3 gene and advanced AMD
Association between SNP rs2230205 of C3 gene and advanced AMD
Association between SNP rs2250656 of C3 gene and advanced AMD
Heterogeneity test and sensitivity analysis
Publication bias
Polymorphism | Number of publication | Publication bias | |
---|---|---|---|
Begg’s test | Egger’s test | ||
rs2230199 | 36 | 0.653 | 0.790 |
rs1047286 | 13 | 0.428 | 0.124 |
rs2230205 | 5 | 1.000 | 0.905 |
rs2250656 | 5 | 1.000 | 0.594 |