Association of Allelic Variants of the Reelin Gene with Autistic Spectrum Disorder: A Systematic Review and Meta-Analysis of Candidate Gene Association Studies
Abstract
:1. Introduction
2. Materials and Methods
2.1. Inclusion Criteria
2.2. Bibliographic Search and Data Extraction
2.3. Statistical Analysis
3. Results
3.1. Study Identification and Selection
3.2. Relationship of Reelin Gene Polymorphisms with ASD
3.3. Relationship of Polymorphic Trinucleotide Repeat (CGG/GCC) within the Reelin Gene with ASD
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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First Author, Year | N | Number of CGG Repeats | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
3/10 | 4/8 | 4/10 | 6/10 | 7/8 | 7/10 | 8/8 | 8/9 | 8/10 | 8/11 | 8/11-15 | 8/12 | 8/13 | 8/14 | 9/10 | 9/13 | 10/10 | ||||
(Persico et al., 2001) [20] | 1. Patients with ASD a | 95 | 1 | 1 | 16 | 44 | 0 | 5 | 2 | 0 | 16 | |||||||||
2. Healthy controls | 186 | 0 | 0 | 36 | 85 | 3 | 1 | 3 | 1 | 48 | ||||||||||
(Zhang et al., 2002) [37] | 1. Patients with ASD 2. Healthy controls | 126 347 | 0 1 | 1 0 | 0 1 | 0 1 | 1 0 | 16 60 | 0 2 | 44 138 | 8 16 | 1 1 | 1 0 | 40 97 | ||||||
(Dutta el al., 2007) [38] | 1. Patients with ASD 2. Healthy controls | 55 80 | 0 1 | 10 12 | 31 42 | |||||||||||||||
First Author, Year | N | Number of CGG Repeats | ||||||||||||||||||
10/11 | 10/11-16 | 10/12 | 10/13 | 10/23 | 12/10 | 12/12 | 12/13 | 13/8 | 13/10 | 13/13 | 14/10 | 15/10 | 16/10 | |||||||
(Persico et al., 2001) [20] | 1. Patients with ASD a | 95 | 0 | 5 | 3 | 1 | 1 | |||||||||||||
2. Healthy controls | 186 | 1 | 2 | 6 | 0 | 0 | ||||||||||||||
(Zhang et al., 2002) [37] | 1. Patients with ASD 2. Healthy controls | 126 347 | 14 28 | 0 2 | ||||||||||||||||
(Dutta el al., 2007) [38] | 1. Patients with ASD 2. Healthy controls | 55 80 | 0 3 | 2 4 | 11 14 | 1 1 | 0 1 | 0 1 | 0 1 |
First Author, Year | N | Number of CGG Repeats | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 23 | |||
(Persico et al., 2001) [20] | 1. Patients with ASD a | 95 | 2 | 84 | 86 | 0 | 11 | 6 | 0 | 1 | |||||||
2. Healthy controls | 186 | 0 | 165 | 190 | 4 | 3 | 9 | 1 | 0 | ||||||||
(Zhang et al., 2002) [37] | 1. Patients with ASD | 126 | 0 | 1 | 0 | 1 | 85 | 2 | 140 | 4 | 5 | 13 | 0 | 0 | 1 | ||
2. Healthy controls | 347 | 1 | 0 | 1 | 1 | 277 | 3 | 363 | 7 | 12 | 26 | 1 | 2 | 0 | |||
(Dutta et al., 2007) [38] | 1. Patients with ASD | 55 | 12 | 83 | 0 | 15 | 0 | 0 | 0 | ||||||||
2. Healthy controls | 80 | 18 | 116 | 3 | 20 | 1 | 1 | 1 |
First Author, Year | N | rs736707 (intron 59) | rs362691(exon22) L997V | rs2229864 (exon 50) | |||||||||||||
Genotype distribution | Allele distribution | Genotype distribution | Allele distribution | Genotype distribution | Allele distribution | ||||||||||||
CC | CT | TT | C | T | CC | CG | GG | C | G | TT | CT | CC | T | C | |||
(Dutta et al., 2007) [38] | 1. Patients with ASD a | 55 | 4 | 24 | 27 | 32 | 78 | ||||||||||
2. Healthy controls | 80 | 8 | 31 | 41 | 47 | 113 | |||||||||||
(Dutta et al., 2008) [23] | 1. Patients with ASD | 77 | 11 | 34 | 32 | 56 | 98 | 56 | 20 | 1 | 132 | 22 | |||||
2. Healthy controls (exon 22 N= 100) | 101 | 19 | 49 | 33 | 87 | 115 | 76 | 23 | 1 | 175 | 25 | ||||||
(Li et al., 2008) [39] | 1. Patients with ASD (intron 59 N= 210) | 213 | 52 | 108 | 50 | 212 | 208 | 159 | 47 | 7 | 365 | 61 | 8 | 76 | 129 | 92 | 334 |
2. Healthy controls | 160 | 29 | 78 | 53 | 136 | 184 | 125 | 30 | 5 | 280 | 40 | 7 | 53 | 100 | 67 | 253 | |
(He et al., 2011) [24] | 1. Patients with ASD (exon 22 N= 219) | 221 | 50 | 116 | 55 | 216 | 226 | 180 | 36 | 3 | 396 | 42 | 9 | 73 | 139 | 92 | 350 |
2. Healthy controls (exon 22 N= 277) (exon 50 N= 278) | 282 | 48 | 146 | 88 | 242 | 322 | 216 | 53 | 8 | 485 | 69 | 13 | 87 | 178 | 113 | 443 | |
(Sharma et al., 2013) [22] | 1. Patients with ASD (intron 59 N= 129) | 136 | 14 | 50 | 65 | 78 | 180 | 3 | 16 | 117 | 22 | 250 | |||||
2. Healthy controls (intron 59 N= 208) | 193 | 35 | 94 | 79 | 164 | 252 | 2 | 34 | 157 | 38 | 348 | ||||||
(Mehdizadeh et al., 2015) [40] | 1. Patients with ASD | 74 | 41 | 26 | 7 | 108 | 40 | ||||||||||
2. Healthy controls | 86 | 52 | 28 | 6 | 132 | 40 | |||||||||||
(Mehdizadeh et al., 2016) [41] | 1. Patients with ASD | 74 | 0 | 16 | 58 | 16 | 132 | ||||||||||
2. Healthy controls | 88 | 0 | 28 | 60 | 28 | 148 | |||||||||||
(Wang et al., 2018) [43] | 1. Patients with ASD | 157 | 33 | 78 | 46 | 144 | 170 | 19 | 70 | 68 | 108 | 206 | |||||
2. Healthy controls | 256 | 54 | 126 | 76 | 234 | 278 | 13 | 76 | 167 | 102 | 410 | ||||||
(Şahin et al., 2018) [42] | 1. Patients with ASD | 61 | 0 | 10 | 51 | 10 | 112 | ||||||||||
2. Healthy controls | 64 | 0 | 8 | 56 | 8 | 120 |
First Author, Year | Country | Criteria for ASD a Definition | Ethnicity | Female/Male Ratio | Age (Mean [SD]) | ||
---|---|---|---|---|---|---|---|
Patients with ASD | Healthy Controls | Patients with ASD | Healthy Controls | ||||
Persico et al., 2001 [20] | Italy | DSM–IV b criteria for Autistic disorder | Caucasian | 6/89 | 89/97 | 6.25 (2.8) | 51.7 (19.6) |
Zhang et al., 2002 [37] | Canada | ADI–R c algorithm / ADOS d | N/A e | N/A | 170/177 | N/A | N/A |
Dutta et al., 2007 [38] | India | DSM–IV criteria for Autistic disorder | Indian | N/A | N/A | N/A | N/A |
Dutta et al., 2008 [23] | India | DSM–IV criteria for Autistic disorder | Indian | 13/64 | N/A | 5.8 (2.9) | N/A |
Li et al., 2008 [39] | China | DSM–IV criteria for Autistic disorder or ICD-10 f | Chinese Han | 32/181 | 25/135 | 5.3 (N/A) | 6.7 (N/A) |
He et al., 2011 [24] | China | DSM–IV criteria for Autistic disorder | Chinese Han | 35/197 | 43/240 | N/A | 32.8 (10.5) |
Sharma et al., 2013 [22] | South Africa | DSM–IV criteria for Autistic disorder | Black, white, and mixed ancestry | N/A | N/A | N/A | N/A |
Mehdizadeh et al., 2015 [40] | Iran | DSM–IV criteria for Autistic disorder | Caucasian | 18/53 | 65/21 | 8.57 (N/A) | N/A |
Mehdizadeh et al., 2016 [41] | Iran | DSM–IV criteria for Autistic disorder | Caucasian | 18/53 | 66/22 | 8.57 (0.07) | 7.79 (0.14) |
Wang et al., 2018 [43] | China | DSM–IV criteria for Autistic disorder | Chinese Han | 21/108 | 72/184 | 8.4 (3.9) | 8.3 (3.9) |
Şahin et al., 2018 [42] | Turkey | g DSM–5 criteria for Autistic disorder | N/A | 5/56 | 12/52 | 5.54 (3.1) | 6.43 (4.0) |
Polymorphisms | OR | 95% CI | Poverall effect | Q | Pheterogeneity |
---|---|---|---|---|---|
Exon 22 | |||||
C vs. G | 0.95 | 0.76, 1.20 | 0.68 | 5.32 | 0.38 |
CC vs. CG + GG | 1.03 | 0.77, 1.38 | 0.83 | 2.85 | 0.42 |
GG vs. CG + CC | 1.20 | 0.83, 1.75 | 0.34 | 4.08 | 0.54 |
Exon 50 | |||||
C vs. T | 0.81 | 0.55, 1.19 | 0.28 | 13.56 | 0.004 |
CC vs. CT + TT | 0.75 | 0.48, 1.16 | 0.19 | 11.50 | 0.009 |
TT vs. CT + CC | 1.18 | 0.61, 2.26 | 0.63 | 5.70 | 0.13 |
Intron 59 | |||||
C vs. T | 0.98 | 0.77, 1.24 | 0.84 | 16.05 | 0.007 |
CC vs. CT + TT | 1.02 | 0.76, 1.37 | 0.88 | 7.84 | 0.17 |
TT vs. CT + CC | 1.02 | 0.73, 1.44 | 0.90 | 13.08 | 0.02 |
Triplet repeat number | |||||
4 | 9.09 | 1.00, 82.50 | 0.05 | 0.01 | 0.94 |
8 | 0.86 | 0.69, 1.08 | 0.19 | 1.30 | 0.52 |
10 | 1.00 | 0.78, 1.29 | 0.98 | 2.77 | 0.25 |
11 | 0.89 | 0.14, 5.59 | 0.90 | 1.63 | 0.20 |
12 | 1.68 | 0.30, 9.50 | 0.56 | 7.41 | 0.02 |
13 | 1.26 | 0.81, 1.97 | 0.31 | 0.22 | 0.89 |
14 | 0.66 | 0.10, 4.20 | 0.66 | 0.08 | 0.96 |
15 | 0.52 | 0.06, 4.69 | 0.56 | 0.00 | 0.95 |
16 | 2.00 | 0.12, 32.62 | 0.63 | 1.52 | 0.22 |
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Hernández-García, I.; Chamorro, A.-J.; Ternavasio-de la Vega, H.G.; Carbonell, C.; Marcos, M.; Mirón-Canelo, J.-A. Association of Allelic Variants of the Reelin Gene with Autistic Spectrum Disorder: A Systematic Review and Meta-Analysis of Candidate Gene Association Studies. Int. J. Environ. Res. Public Health 2020, 17, 8010. https://doi.org/10.3390/ijerph17218010
Hernández-García I, Chamorro A-J, Ternavasio-de la Vega HG, Carbonell C, Marcos M, Mirón-Canelo J-A. Association of Allelic Variants of the Reelin Gene with Autistic Spectrum Disorder: A Systematic Review and Meta-Analysis of Candidate Gene Association Studies. International Journal of Environmental Research and Public Health. 2020; 17(21):8010. https://doi.org/10.3390/ijerph17218010
Chicago/Turabian StyleHernández-García, Ignacio, Antonio-Javier Chamorro, Hugo Guillermo Ternavasio-de la Vega, Cristina Carbonell, Miguel Marcos, and José-Antonio Mirón-Canelo. 2020. "Association of Allelic Variants of the Reelin Gene with Autistic Spectrum Disorder: A Systematic Review and Meta-Analysis of Candidate Gene Association Studies" International Journal of Environmental Research and Public Health 17, no. 21: 8010. https://doi.org/10.3390/ijerph17218010