Highlights
Introduction
Materials and methods
Search strategy and study selection
Eligibility criteria
Data abstraction
Statistical analysis
Results
Study selection
Study characteristics
First author, publication year | Country | Ethnicity | Mean age, years (Case/ Control) | Age group of individuals | Genotyping method | DMFT score (Case/Control) | Polymorphisms |
---|---|---|---|---|---|---|---|
Ouryouji, 2008 [13] | Japan | Asian | 5.4/4.8 | Children | PCR-RFLP | ≥10/0 | ENAM rs3796703 AMELX rs6639060 AMELX rs2106416 |
Azevedo, 2010 [16] | Brazil | Caucasian | 12 | Children | PCR-SSCP | ≥1/0 | LTF rs1126478 |
Kang, 2011a [17] | Korea | Asian | 21.3/23.2 | Adults | PCR | > 2/≤2 | AMELX rs17878486 |
Olszowski, 2012ab [18] | Poland | Caucasian | 5 | Children | PCR-RFLP | ≥3/< 3 | AMELX rs2106416 |
13 | Children | PCR-RFLP | ≥3/< 3 | AMELX rs2106416 | |||
Gasse, 2013 [12] | France | Caucasian | 7.6/22 | Both | PCR | ≥4/0 | AMELX rs946252 |
Jeremias, 2013a [11] | Brazil | Mixed | Case: < 6 Control: < 20 | Children | RT-PCR | ≥4/≤3 | ENAM rs1264848 ENAM rs3796704 AMELX rs946252 AMELX rs17878486 |
Ergöz, 2014 [19] | Turkey | Caucasian | 8.7/8.7 | Children | TaqMan | ≥1/0 | ENAM rs1264848 ENAM rs3796704 AMELX rs946252 AMELX rs17878486 |
Volckova, 2014 [20] | Czech | Caucasian | Range: 11–13 | Children | PCR-RFLP | ≥1/0 | LTF rs1126478 |
Gerreth, 2016 [14] | Poland | Caucasian | 2.6 | Children | RT-PCR | ≥1/0 | ENAM rs1264848 |
Yildiz, 2016a [21] | Turkey | Caucasian | Range: 20–60 | Adults | PCR-RFLP | ≥14/≤5 | AMELX rs6639060 |
Gerreth, 2017 [15] | Poland | Caucasian | Range: 1.7–3.5 | Children | TaqMan | ≥1/0 | AMELX rs17878486 |
Wang, 2017 [5] | China | Asian | 3.5/3.7 | Children | PCR | ≥4/0 | LTF rs1126478 ENAM rs3796703 |
Borilova Linhartova, 2018a [22] | Czech | Caucasian | Range: 13–15 | Children | TaqMan | ≥1/0 | ENAM rs1264848 |
Koohpeima, 2018a [23] | Iran | Caucasian | 29.8/28.4 | Adults | ARMS-PCR | NA | ENAM rs3796704 |
Wang, 2018 [24] | China | Asian | Range: 2–4 | Children | PCR | ≥8/0 | LTF rs1126478 |
Devang Divakar, 2019 [25] | Saudi Arabia | Caucasian | 6.9/23.2 | Both | RT-PCR | ≥4/0 | ENAM rs1264848 ENAM rs3796704 |
First author, publication year | LTF rs1126478a | ENAM s1264848a | ENAM rs3796704a | ENAM rs3796703b | P-value of HWE for controls | ||||
---|---|---|---|---|---|---|---|---|---|
Case | Control | Case | Control | Case | Control | Case | Control | ||
Ouryouji, 2008 [13] | NA | NA | NA | NA | NA | NA | 76/4/0 | 59/8/0 | 0.603 |
Azevedo, 2010 [16] | 16/30/16 | 19/22/7 | NA | NA | NA | NA | NA | NA | 0.877 |
Jeremias, 2013 [11] | NA | NA | 13/44/20 | 21/41/20 | 4/11/61 | 1/19/57 | NA | NA | 0.999/0.676 |
Ergöz, 2014 [19] | NA | NA | 4/41/55 | 1/35/64 | 0/16/78 | 1/27/69 | NA | NA | 0.108/0.351 |
Volckova, 2014 [20] | 288/150/44 | 86/56/13 | NA | NA | NA | NA | NA | NA | 0.374 |
Gerreth, 2016 [14] | NA | NA | 8/37/3 | 4/26/18 | NA | NA | NA | NA | 0.202 |
Wang, 2017 [5] | 64/222/219 | 64/209/227 | NA | NA | NA | NA | 439/64/2 | 458/42/0 | 0.149/0.327 |
Borilova Linhartova, 2018 [22] | NA | NA | 45/259/237 | 19/74/84 | NA | NA | NA | NA | 0.656 |
Koohpeima, 2018 [23] | NA | NA | NA | NA | 0/32/204 | 0/20/146 | NA | NA | 0.409 |
Wang, 2018 [24] | 63/224/220 | 51/168/184 | NA | NA | NA | NA | NA | NA | 0.196 |
Devang Divakar, 2019 [25] | NA | NA | 89/58/21 | 116/68/9 | 11/58/99 | 25/76/92 | NA | NA | 0.809/0.146 |
First author, publication year | AMELX rs946252b | AMELX rs17878486b | AMELX rs6639060b | AMELX rs2106416b | P-value of HWE for controls | ||||
Case | Control | Case | Control | Case | Control | Case | Control | ||
Ouryouji, 2008 [13] | NA | NA | NA | NA | 80/0/0 | 67/0/0 | 78/2/0 | 16/6/0 | NA/0.458 |
Kang, 2011 [17] | NA | NA | 1/2/82 | 0/2/29 | NA | NA | NA | NA | 0.852 |
Olszowski, 2012 (i) [18] | NA | NA | NA | NA | NA | NA | 24/13/0 | 21/12/1 | 0.643 |
Olszowski, 2012 (ii) [18] | NA | NA | NA | NA | NA | NA | 26/26/6 | 28/20/2 | 0.495 |
Gasse, 2013 [12] | 5/9/25 | 4/1/25 | NA | NA | NA | NA | NA | NA | < 0.0001 |
Jeremias, 2013 [11] | 61/12/5 | 63/13/5 | 4/15/57 | 15/11/56 | NA | NA | NA | NA | 0.002/< 0.0001 |
Ergöz, 2014 [19] | 5/18/11 | 10/17/9 | 8/18/14 | 3/21/8 | NA | NA | NA | NA | 0.742/0.051 |
Yildiz, 2016 [21] | NA | NA | NA | NA | 54/11/12 | 56/9/12 | NA | NA | < 0.0001 |
Gerreth, 2017 [15] | NA | NA | 8/10/30 | 31/14/3 | NA | NA | NA | NA | 0.422 |
Pooled analysis
Polymorphism, (number of studies) | G vs. A | GG vs. AA | AG vs. AA | AG + GG vs. AA | GG vs. AA + AG |
---|---|---|---|---|---|
OR (95%CI), P-value, I2 (%), Ph | OR (95%CI), P-value, I2 (%), Ph | OR (95%CI), P-value, I2 (%), Ph | OR (95%CI), P-value, I2 (%), Ph | OR (95%CI), P-value, I2 (%), Ph | |
LTF rs1126478 (n = 4) | 0.98 (0.87, 1.10), 0.68, 25, 0.26 | 1.03 (0.80, 1.33), 0.82, 4, 0.37 | 1.00 (0.80, 1.25), 0.99, 4, 0.44 | 0.99 (0.81, 1.23), 0.96, 7, 0.36 | 0.95 (0.80, 1.13), 0.58, 0, 0.45 |
ENAM rs1264848 (n = 5) | 0.93 (0.65, 1.32), 0.68, 75, 0.003 | 0.88 (0.34, 2.30), 0.79, 76, 0.002 | 1.21 (0.88, 1.65), 0.24, 0, 0.48 | 1.24 (0.93, 1.67), 0.15, 24, 0.26 | 0.83 (0.44, 1.58), 0.58, 79, 0.0007 |
ENAM rs3796704 (n = 4) | 1.38 (1.08, 1.76), 0.009, 27, 0.25 | 1.86 (0.96, 3.62), 0.07, 44, 0.17 | 1.27 (0.64, 2.52), 0.49, 50, 0.13 | 1.64 (0.86, 3.14), 0.13, 43, 0.17 | 1.41 (1.06, 1.87), 0.02, 18, 0.30 |
Polymorphism, (number of studies) | T vs. C | TT vs. CC | CT vs. CC | CT + TT vs. CC | TT vs. CC + CT |
OR (95%CI), P-value, I2 (%), Ph | OR (95%CI), P-value, I2 (%), Ph | OR (95%CI), P-value, I2 (%), Ph | OR (95%CI), P-value, I2 (%), Ph | OR (95%CI), P-value, I2 (%), Ph | |
ENAM rs3796703 (n = 2) | 0.92 (0.24, 3.58), 0.91, 78, 0.03 | 5.22 (0.25, 108.96), 0.29 | 0.89 (0.23, 3.48), 0.87, 77, 0.04 | 0.90 (0.23, 3.63), 0.89, 78, 0.03 | 2.90 (0.92, 9.12), 0.07, 0, 0.69 |
AMELX rs946252 (n = 3) | 1.01 (0.68, 1.51), 0.95, 39, 0.20 | 1.27 (0.58, 2.75), 0.55, 0, 0.51 | 1.45 (0.75, 2.81), 0.27, 31, 0.23 | 1.21 (0.68, 2.14), 0.52, 0, 0.51 | 0.82 (0.43, 1.56), 0.54, 0.38, 0.20 |
AMELX rs17878486 (n = 4) | 2.25 (0.81, 6.24), 0.12, 86, 0.0001 | 3.59 (0.55, 23.32), 0.18, 81, 0.001 | 1.45 (0.36, 5.80), 0.60, 0.67, 0.03 | 2.30 (0.51, 10.33), 0.28, 77, 0.004 | 3.10 (0.85, 11.28), 0.09, 81, 0.001 |
AMELX rs6639060 (n = 2) | 1.08 (0.63, 1.85), 0.78 | 1.04 (0.43, 2.51), 0.94 | 1.27 (0.49, 3.30), 0.63 | 1.14 (0.56, 2.29), 0.72 | 1.00 (0.42, 2.39), 1.00 |
AMELX rs2106416 (n = 3) | 0.59 (0.16, 2.11), 0.41, 82, 0.003 | 1.83 (0.47, 7.06), 0.38, 40, 0.20 | 0.55 (0.13, 2.25), 0.40, 80, 0.006 | 0.59 (0.15, 2.31), 0.45, 79, 0.008 | 1.67 (0.44, 6.34), 0.45, 31, 0.23 |
Subgroup analysis
Polymorphism, (number of studies) | G vs. A | GG vs. AA | AG vs. AA | AG + GG vs. AA | GG vs. AA + AG |
---|---|---|---|---|---|
OR (95%CI), P-value, I2 (%), Ph | OR (95%CI), P-value, I2 (%), Ph | OR (95%CI), P-value, I2 (%), Ph | OR (95%CI), P-value, I2 (%), Ph | OR (95%CI), P-value, I2 (%), Ph | |
LTF rs1126478 | |||||
Ethnicity | |||||
Caucasian (2) | 1.18 (0.66, 2.11), 0.58, 73, 0.05 | 1.49 (0.58, 3.85), 0.41, 55, 0.13 | 1.02 (0.53, 1.97), 0.95, 53, 0.14 | 1.16 (0.53, 1.97), 0.95, 0.53, 0.14 | 1.33 (0.77, 2.29), 0.30, 6, 0.30 |
Asian (2) | 0.96 (0.84, 1.09), 0.52, 0, 0.98 | 0.97 (0.73, 1.29), 0.81, 0, 0.99 | 1.07 (0.80, 1.43), 0.64, 0, 0.96 | 1.02 (0.78, 1.33), 0.91, 0, 0.97 | 0.92 (0.77, 1.10), 0.35, 0, 0.96 |
Age group | |||||
Children (4) | 0.98 (0.87, 1.10), 0.68, 25, 0.26 | 1.03 (0.80, 1.33), 0.82, 4, 0.37 | 1.00 (0.80, 1.25), 0.99, 4, 0.44 | 0.99 (0.81, 1.23), 0.96, 7, 0.36 | 0.95 (0.80, 1.13), 0.58, 0, 0.45 |
Control group | |||||
Caries free (4) | 0.98 (0.87, 1.10), 0.68, 25, 0.26 | 1.03 (0.80, 1.33), 0.82, 4, 0.37 | 1.00 (0.80, 1.25), 0.99, 4, 0.44 | 0.99 (0.81, 1.23), 0.96, 7, 0.36 | 0.95 (0.80, 1.13), 0.58, 0, 0.45 |
ENAM rs1264848 | |||||
Ethnicity | |||||
Caucasian (4) | 0.86 (0.56, 1.32), 0.49, 80, 0.002 | 0.67 (0.18, 2.45), 0.54, 82, 0.0009 | 1.13 (0.80, 1.59), 0.48, 0, 0.45 | 1.18 (0.86, 1.62), 0.31, 35, 0.20 | 0.76 (0.34, 1.72), 0.51, 84, 0.0003 |
Mixed (1) | 1.23 (0.79,1.91), 0.36 | 1.62 (0.64, 4.09), 0.31 | 1.73 (0.77, 3.90), 0.18 | 1.69 (0.78, 3.68), 0.18 | 1.09 (0.53, 2.23), 0.82 |
Age group | |||||
Children (4) | 0.82 (0.57, 1.18), 0.28, 67, 0.03 | 0.58 (0.19, 1.82), 0.35, 74, 0.01 | 1.30 (0.84, 2.01), 0.26, 3, 0.36 | 1.16 (0.76, 1.75), 0.49, 42, 0.16 | 0.66 (0.37, 1.17), 0.15, 70, 0.02 |
Control group | |||||
Caries free (3) | 0.79 (0.39, 1.63), 0.53, 86, 0.0006 | 0.42 (0.03, 5.41), 0.51, 88, 0.0003 | 1.00 (0.66, 1.51), 1.00, 0, 0.44 | 0.74 (0.27, 2.02), 0.56, 55, 0.11 | 0.66 (0.15, 2.95), 0.59, 89, < 0.0001 |
Low caries (2) | 1.03 (0.83, 1.29), 0.78, 0, 0.37 | 1.30 (0.79, 2.14), 0.30, 0, 0.59 | 1.57 (0.97, 2.53), 0.07, 0, 0.76 | 1.45 (0.92, 2.28), 0.11, 0, 0.62 | 0.90 (0.66, 1.23), 0.51, 0, 0.57 |
ENAM rs3796704 | |||||
Ethnicity | |||||
Caucasian (3) | 1.43 (1.10, 1.85), 0.007, 45, 0.16 | 2.49 (1.19, 5.24), 0.02, 0, 0.85 | 1.74 (0.81, 3.74), 0.16, 0, 0.98 | 2.16 (1.05, 4.45), 0.04, 0, 0.85 | 1.41 (1.04, 1.91), 0.03, 45, 0.16 |
Mixed (1) | 1.11 (0.57, 2.15), 0.77 | 0.27 (0.03, 2.47), 0.24 | 0.14 (0.01, 1.46), 0.10 | 0.24 (0.03, 2.17), 0.20 | 1.43 (0.67, 3.05), 0.36 |
Age group | |||||
Children (2) | 1.46 (0.92, 2.32), 0.11, 22, 0.26 | 0.61 (0.13, 2.93), 0.54, 38, 0.20 | 0.35 (0.07, 1.74), 0.20, 35, 0.22 | 0.54 (0.11, 2.56), 0.44, 37, 0.21 | 1.71 (1.02, 2.85), 0.04, 0, 0.53 |
Control group | |||||
Caries free (2) | 1.62 (1.21, 2.17), 0.001, 0, 0.59 | 2.499 (1.19, 5.24), 0.02, 0, 0.85 | 1.74 (0.81, 3.74), 0.16, 0, 0.98 | 2.16 (1.05, 4.45), 0.04, 0, 0.85 | 1.67 (1.17, 2.39), 0.0050, 0.58 |
Low caries (2) | 0.97 (0.63, 1.50), 0.89, 0, 0.61 | 0.27 (0.03, 2.47), 0.24 | 0.14 (0.01, 1.46), 0.10 | 0.24 (0.03, 2.17), 0.20 | 1.05 (0.66, 1.68), 0.83, 0, 0.32 |
Polymorphism, (number of studies) | T vs. C | TT vs. CC | CT vs. CC | CT + TT vs. CC | TT vs. CC + CT |
OR (95%CI), P-value, I2 (%), Ph | OR (95%CI), P-value, I2 (%), Ph | OR (95%CI), P-value, I2 (%), Ph | OR (95%CI), P-value, I2 (%), Ph | OR (95%CI), P-value, I2 (%), Ph | |
ENAM rs3796703 | |||||
Ethnicity | |||||
Asian (2) | 0.92 (0.24, 3.58), 0.91, 78, 0.03 | 5.22 (0.25, 108.96), 0.29 | 0.89 (0.23, 3.48), 0.87, 77, 0.04 | 0.90 (0.23, 3.63), 0.89, 78, 0.03 | 2.90 (0.92, 9.12), 0.07, 0, 0.69 |
Age group | |||||
Children (2) | 0.92 (0.24, 3.58), 0.91, 78, 0.03 | 5.22 (0.25, 108.96), 0.29 | 0.89 (0.23, 3.48), 0.87, 77, 0.04 | 0.90 (0.23, 3.63), 0.89, 78, 0.03 | 2.90 (0.92, 9.12), 0.07, 0, 0.69 |
AMELX rs946252 | |||||
Ethnicity | |||||
Caucasian (2) | 0.95 (0.35, 2.55), 0.92, 69, 0.07 | 1.42 (0.54, 3.76), 0.48, 17, 0.27 | 2.80 (0.93, 8.43), 0.07, 0, 0.38 | 1.63 (0.67, 4.01), 0.28, 0, 0.42 | 0.73 (0.19, 2.87), 0.66, 67, 0.08 |
Mixed (1) | 0.99 (0.53, 1.86), 0.98 | 1.03 (0.28, 3.75), 0.96 | 0.95 (0.40, 2.25), 0.91 | 0.98 (0.46, 2.07), 0.95 | 1.04 (0.29, 3.75), 0.95 |
Age group | |||||
Children (2) | 1.21 (0.77,1.91), 0.42, 0, 0.37 | 1.54 (0.61, 3.92), 0.36, 0, 0.37 | 1.24 (0.61, 2.49), 0.56, 5, 0.31 | 1.24 (0.66, 2.33), 0.50, 24, 0.25 | 1.26 (0.56, 2.83), 0.25 |
Control group | |||||
Caries free (2) | 0.95 (0.35, 2.55), 0.92, 69, 0.07 | 1.42 (0.54, 3.76), 0.48, 17, 0.27 | 2.80 (0.93, 8.43), 0.07, 0, 0.38 | 1.63 (0.67, 4.01), 0.28, 0, 0.42 | 0.73 (0.19, 2.87), 0.66, 67, 0.08 |
Low caries (1) | 0.99 (0.53, 1.86), 0.98 | 1.03 (0.28, 3.75), 0.96 | 0.95 (0.40, 2.25), 0.91 | 0.98 (0.46, 2.07), 0.95 | 1.04 (0.29, 3.75), 0.95 |
AMELX rs17878486 | |||||
Ethnicity | |||||
Caucasian (2) | 2.87 (0.35, 23.23), 0.32, 95, < 0.0001 | 5.12 (0.09, 278.85), 0.42, 93, 0.0002 | 1.00 (0.12, 8.23), 1.00, 0.81, 0.02 | 2.03 (0.10, 42.44), 0.65, 92, 0.0004 | 6.17 (0.41, 92.05), 0.19, 91, 0.001 |
Asian (1) | 1.38 (0.25, 7.75), 0.71 | 0.93 (0.04, 23.52), 0.97 | 0.33 (0.01, 12.82), 0.56 | 0.89 (0.04, 22.53), 0.95 | 1.89 (0.30, 11.85), 0.50 |
Mixed (1) | 1.87 (1.06, 3.30), 0.03 | 3.82 (1.19, 12.21), 0.02 | 5.11 (1.33, 19.72), 0.02 | 4.03 (1.27, 12.75), 0.02 | 1.39 (0.69, 2.80), 0.35 |
Age group | |||||
Children (3) | 2.48 (0.76, 8.05), 0.13, 90, < 0.0001 | 4.69 (0.55, 40.16), 0.16, 86, 0.0007 | 1.72 (0.37, 7.92), 0.48, 75, 0.02 | 2.65 (0.49, 14.35), 0.26, 84, 0.002 | 3.55 (0.72, 17.60), 0.12, 87, 0.0004 |
Adults (1) | 1.38 (0.25, 7.75), 0.71 | 0.93 (0.04, 23.52), 0.97 | 0.33 (0.01, 12.82), 0.56 | 0.89 (0.04, 22.53), 0.95 | 1.89 (0.30, 11.58), 0.50 |
Control group | |||||
Caries free (2) | 2.87 (0.35, 23.23), 0.32, 95, < 0.0001 | 5.12 (0.09, 278.85), 0.42, 93, 0.0002 | 1.00 (0.12, 8.23), 1.00, 0.81, 0.02 | 2.03 (0.10, 42.44), 0.65, 92, 0.0004 | 6.17 (0.41, 92.05), 0.19, 91, 0.001 |
Low caries (2) | 1.82 (1.06, 3.11), 0.03, 0, 0.74 | 3.28 (1.14, 9.43), 0.03, 0, 0.42 | 3.42 (1.04, 11.28), 0.04, 47, 0.17 | 3.43 (1.21, 9.75), 0.02, 0, 0.39 | 1.44 (0.75, 2.77), 0.27, 0, 0.76 |
AMELX rs6639060 | |||||
Ethnicity | |||||
Caucasian (1) | 1.08 (0.63, 1.85), 0.78 | 1.04 (0.43, 2.51), 0.94 | 1.27 (0.49,3.30), 0.63 | 1.14 (0.56, 2.29), 0.72 | 1.00 (0.42, 2.39), 1.00 |
Age group | |||||
Adults (1) | 1.08 (0.63, 1.85), 0.78 | 1.04 (0.43, 2.51), 0.94 | 1.27 (0.49,3.30), 0.63 | 1.14 (0.56, 2.29), 0.72 | 1.00 (0.42, 2.39), 1.00 |
AMELX rs2106416 | |||||
Ethnicity | |||||
Caucasian (2) | 1.25 (0.77, 2.03), 0.37, 30, 0.23 | 1.83 (0.47, 7.06), 0.38, 40, 0.20 | 1.20 (0.65, 2.22), 0.56, 0, 0.54 | 1.25 (0.69, 2.27), 0.46, 0, 0.35 | 1.67 (0.44, 6.34), 0.45, 31, 0.23 |
Age group | |||||
Children (3) | 0.59 (0.16, 2.11), 0.41, 82, 0.003 | 1.83 (0.47, 7.06), 0.38, 40, 0.20 | 0.55 (0.13, 2.25), 0.40, 80, 0.006 | 0.59 (0.15, 2.31), 0.45, 79, 0.008 | 1.67 (0.44, 6.34), 0.45, 31, 0.23 |