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Associations of endocrine stress‐related gene polymorphisms with risk of autism spectrum disorders: Evidence from an integrated meta‐analysis
Author(s) -
Yang Pingyuan,
Menga Yajing,
Li Tao,
Huang Yi
Publication year - 2017
Publication title -
autism research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.656
H-Index - 66
eISSN - 1939-3806
pISSN - 1939-3792
DOI - 10.1002/aur.1822
Subject(s) - rs4680 , meta analysis , autism , 5 httlpr , medicine , clinical psychology , catechol o methyl transferase , serotonin transporter , psychology , psychiatry , allele , genetics , biology , gene , serotonin , receptor
Autism spectrum disorders (ASD) are related to serotonin transporter (5‐HTT) and catechol‐O‐methyl transferase (COMT) as two most monoaminergic polymorphic variations. However, multiple studies assessing rs4680 and 5‐HTTLPR variants in ASD have reported inconsistent results. Therefore, we conducted an integrated meta‐analysis to combine case‐control and transmission/disequilibrium test (TDT) studies to determine whether COMT and 5‐HTT are associated with ASD. We searched multiple electronic databases (PubMed, EmBase and Web of Science) to identify studies assessing the rs4680 and 5‐HTTLPR variants in ASD from Jan 1997 to Dec 2016. Then allelic data from case–control and TDT studies were analyzed by the Catmap package in the R software. A total of 5 studies were eligible for the meta‐analysis of rs4680, including 3 case–control, 1 TDT and 1 TDT & case–control studies. Meanwhile, 22 studies of 5‐HTTLPR were available, including 16 TDT, 4 case–control and 2 TDT & case–control studies. The current meta‐analysis included 814 ASD cases, 741 controls and 311 families related to rs4680; 749 ASD cases, 1,118 controls and 1,861 families relevant to 5‐HTTLPR were also evaluated. For rs4680, the pooled OR was 1.18 (95% CI = 0.87–1.59, P = 0.29, P heterogeneity < 0.00001). There was no significant association of rs4680 with risk of ASD between the two subgroups. For 5‐HTTLPR, the pooled OR was 1.05 (95% CI = 0.92–1.20, P = 0.4652, P heterogeneity < 0.00001). Meanwhile, we found no significant risk in individual case–control or TDT studies. The above findings indicated that neither COMT rs4680 nor 5‐HTT 5‐HTTLPR polymorphism significantly affects ASD risk. Autism Res 2017, 10: 1722–1736 . © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Our results showed no evidence of significant association of either COMT rs4680 or 5‐HTT 5‐HTTLPR variants with ASD, showing that these two genes may not be major susceptible genetic factors in ASD occurrence, and may have a reciprocal action with each other in combination with environmental factors. These findings further provide evidence that a single gene variant may not dictate autism occurrence, but possibly contributes to a specific phenotype or subtype of ASD.