Objective:This case-control study aimed to determine the correlation between single nucleotide polymorphisms (SNPs) in the neurotransmitter transporter genes SLC6A3 and SLC6A4 and childhood autism spectrum disorder (ASD), as well as the severity of the disease. Patients and Methods:Children with ASD and age- and sex-matched healthy controls were recruited from a hospital and schools, respectively. Seven SNPs in the SLC6A3 gene and three SNPs in the SLC6A4 gene were analyzed in blood cell DNA using the TaqMan probe approach. The severity of the disease was evaluated using the Childhood Autism Rating Scale (CARS). Results:A total of 249 children with ASD and 343 controls were included. The genotype frequencies of the examined SNPs were not correlated with childhood ASD. Only the T allele of the SNP rs140700 displayed a non-significant association with a reduced risk of childhood ASD (OR = 0.6, 95% CI: 0.4-1.0, P = 0.0517). Interestingly, the C allele of rs140701 was significantly correlated with lower disease severity (OR = 0.6, 95% CI: 0.4-0.9, P = 0.0093). Additionally, the genotype of rs27072 was significantly associated with the score of the body use domain of CARS; however, no examined SNPs showed a significant association with the overall score. Conclusion:Certain SNPs on neurotransmitter transporter SLC6A3 and SLC6A4 genes are correlated with the severity of childhood autism spectrum disorder but not with the risk of developing the disease. Further studies are needed to explore the underlying mechanisms and potential clinical applications.

Imbalanced glutamate signaling has been implicated in the development of autism spectrum disorder (ASD). This case-control study was to examine single nucleotide polymorphisms (SNPs) in glutamate receptor and carrier genes and determine their association with childhood ASD in a Chinese Han population. A total of 12 SNPs in genes encoding glutamate receptors (GRM7 and GRM8) and carriers (SLC1A1 and SLC25A12) were examined in 249 autistic children and 353 healthy controls. The Childhood Autism Rating Scale (CARS) and its verbal communication domain were applied to evaluate the severity of the disease and language impairment, respectively. The T allele of rs2292813 in the SLC25A12 gene was significantly associated with an increased risk of ASD (odds ratio (OD) = 1.7, 95

Objective This study aimed to examine the correlation between polymorphisms in vitamin D receptor (VDR) gene and serum vitamin D, and to determine their role in predicting childhood Autism Spectrum Disorder (ASD). Methods Children with ASD and age- and gender- matched healthy controls were recruited from the Chinese Han population. Their serum 25(OH) vitamin D was measured using competitive chemiluminescent immunoassays. The TaqMan probe approach was applied to analyze the common VDR SNPs rs731236 (Taq1), rs11568820 (Cdx2), rs1544410 (BsmI), and rs228570 (FokI). Both linear and logistic regressions were applied in data analysis. Results A total of 269 children with ASD and 320 healthy controls were recruited. Children with ASD had significantly lower levels of serum vitamin D and a significantly higher rate of vitamin D deficiency (< 20 ng/ml) compared to healthy controls (67.7% vs 34.1%). All these examined VDR SNPs were not correlated with serum vitamin D concentrations or vitamin D deficiency. Logistic regression analysis revealed that rs731236 and serum vitamin D were associated with childhood ASD. The area under the receiver operating characteristic (ROC) curve was 0.7285 for serum vitamin D. Children with both T/C genotype of rs731236 and vitamin D deficiency had a higher risk of being diagnosed with ASD. Conclusion All examined common VDR SNPs are not correlated with serum vitamin D concentrations or vitamin D deficiency. The combination of T/C phenotype of rs731236 and vitamin D deficiency are associated with a higher risk of childhood ASD. Vitamin D is a promising target in the prevention and treatment of this disease.

Dysfunctions of the neurotransmitter system are related to the development of many psychological diseases including autism spectrum disorder (ASD). Single nucleotide polymorphisms (SNPs) are correlated with varied susceptibility of ASD and response to treatments. The association between SNPs in genes encoding serotonin and dopamine receptors and childhood ASD was examined in a Chinese Han population. Both autistic children (n = 319) and age-and gender-matched healthy controls (n = 347) were recruited from a local district. Disease severity was evaluated by the childhood autism rating scale (CARS). SNPs of rs6311 and rs6313 in the serotonin receptor HTR2A gene, rs4630328 in the dopamine receptor D2 (DRD2) gene and rs167771 in the DRD3 gene were examined. The CC genotype of rs6311 was significantly associated with an increased risk of ASD (odds ratio (OD) = 1.8 vs TT, 95% confidence interval (CI): 1.2–2.8, P = 0.0085). Carriers of the C allele of rs6311 had a significantly higher risk of childhood ASD (OD =1.3, 95% CI = 1.1–1.7, P = 0.0094). A strong linkage disequilibrium was observed between rs6311 and rs6313 (D′ = 0.93, r2 = 0.86). There were significant correlations between haplotypes (T-A and C-G of rs6311-rs6313) and risk of childhood ASD. In contrast, the frequencies of genotypes and alleles of rs6313, rs4630328 and rs167771 were not significantly different between the case and control groups. All the SNPs examined were not associated with severity of the disease. Our study demonstrates that certain SNPs in the HTR2A gene, but not the DRD2 and DRD3, are associated with susceptibility to childhood ASD.

Objective Genetic factors play an important role in the development of autism spectrum disorder (ASD). This case-control study was to determine the association between childhood ASD and single nucleotide polymorphisms (SNPs) rs3746599 in the DUSP15 gene, rs7794745 in the CNTNAP2 gene, and rs251379 in the PCDHA gene in a Chinese Han population. Methods Genotypes of SNPs were examined in DNA extracted from blood cells from 201 children with ASD and 200 healthy controls. The Children Autism Rating Scale (CARS) was applied to evaluate the severity of the disease and language impairment. The relationship between SNPs and the risk of ASD or the severity of the disease was determined by logistic regression and one-way ANOVA. Results The genotype G/G of rs3746599 in the DUSP15 gene was significantly associated with a decreased risk of ASD (odds ratio (OR) = 0.65, 95% confidence interval (CI): 0.42-0.99, P = 0.0449). The T allele of rs7794745 in the CNTNAP2 gene was associated with an increased risk of ASD (OR = 1.34, 95% CI: 1.01-1.77, P = 0.0435). The SNP rs251379 was not associated with ASD. Though none of the SNPs examined were associated with ASD severity, rs7794745 was associated with severity of language impairment. Conclusions Our findings suggest that both rs3746599 in the DUSP15 gene and rs7794745 in the CNTNAP2 gene are associated with risk of childhood ASD, and rs7794745 is also related to the severity of language impairment in autistic children from a Chinese Han population.

Vitamin D deficiency has been implicated as a risk factor for autism spectrum disorder (ASD). This case-controlled study was to determine the association between single nucleotide polymorphisms (SNPs) in genes encoding vitamin D metabolism related enzymes and childhood ASD in a Chinese Han population. Both autistic children and age-and gender-matched healthy controls were recruited from September 2012-November 2017. The severity of ASD was evaluated by the childhood autism rating scale (CARS). Taqman probe based real-time PCR was applied to examine genotypes. The association between SNPs and the risk of ASD or the disease severity was examined through the logistic regression. This study recruited 249 children with ASD and 353 healthy controls. The G/A genotype (P = 0.0112) or the G allele (P = 0.0117) of CYP24A1 rs17219315, and the G/A genotype of CYP27B1 rs4646536 (P = 0.0341) were significantly associated with an increased risk of ASD. In addition, multivariate analysis found that A allele of both CYP2R1 rs12794714 (P = 0.0159) and CYP27B1 rs4646536 (P = 0.0268) were significantly associated with the severity of ASD. Genetic polymorphisms in vitamin D metabolism related enzymes are associated with the risk of childhood ASD and the severity of the disease.

Background It is inconclusive whether children with autism spectrum disorder (ASD) experience a deficit in facial emotion recognition. The dopaminergic pathway has been implicated in the pathogenesis of ASD. This study was aimed at determining facial emotion recognition and its correlation with polymorphisms in the dopaminergic pathway genes in children with ASD. Methods Facial emotion recognition was examined in 98 children with ASD and 60 age- and gender-matched healthy controls. The severity of ASD was evaluated using the Childhood Autism Rating Scale (CARS). DNA from blood cells was used to analyze the genotypes of single-nucleotide polymorphisms (SNPs) in dopaminergic pathway genes. SNPs of DBH rs1611115, DDC rs6592961, DRD1 rs251937, DRD2 rs4630328, and DRD3 rs167771 were analyzed. Results Children with ASD took a significantly longer time to recognize all facial emotions, and their interpretations were less accurate for anger at low intensity and fear at both low and high intensities. The severity of the disease was associated with significant delays in recognition of all facial emotions and with a decrease in accuracy in recognition of happiness and anger at low intensity. Accuracy in recognizing fear at high intensity and sadness at low intensity was associated with rs251937 and rs4630328, respectively, in children with ASD. Multivariate logistic regression analysis revealed that SNP rs167771, response time for the recognition of happiness, sadness and fear, and accuracy in recognition of anger and fear were all associated with the risk of childhood ASD. Conclusions Children with ASD experience a deficit in facial emotion recognition. Certain SNPs in the dopaminergic pathway genes are associated with accuracy in recognizing selective facial emotions in children with ASD.

Abstract Background: Dysfunction of glutamate signaling has been implicated in the etiology of autism spectrum disorder (ASD). This case-control study was to examine the association between childhood ASD and single nucleotide polymorphisms (SNPs) in genes of the glutamate signaling pathway in a Chinese Han population.Methods: A total of 12 SNPs in the SLC1A1, SLC25A12, GRM7 and GRM8 genes were examined. The Children Autism Rating Scale (CARS) was applied to evaluate the severity of the disease. The relationship between SNPs and the risk of ASD or the severity of the disease was determined by logistic regression.Results: The T allele of rs2292813 in the SLC25A12 gene was significantly associated with an increased risk of ASD (odds ratio (OD) =1.7, 95% confidence interval (CI): 1.1-2.6, P=0.0107). Other examined SNPs were not associated with the risk of ASD. None of the SNPs examined were associated with the severity of ASD.Conclusions: Our findings support the involvement of SNPs in the SLC25A12 gene, but not SNPs in the SLC1A1, GRM7 and DRM8 genes, in the development of childhood ASD in the Chinese Han population.

Both genetic and environmental factors have been implicated in the etiology of autism spectrum disorder (ASD). This case-control study aimed to determine the association of single-nucleotide polymorphisms (SNPs) rs731276 (TaqI), rs1568820 (Cdx2), rs1544410 (BsmI), and rs2228570 (FokI) in the vitamin D receptor (VDR) gene with susceptibility of childhood ASD and severity of the disease. A total of 201 children with ASD and 200 healthy controls from the Han Chinese population were recruited. SNP genotyping was carried out by TaqMan probe-based real-time PCR using genomic DNA extracted from blood cells. Among four examined SNPs, only the CT genotype (odds ratio (OR) = 1.96, 95% confidence interval (CI) = 1.05-3.68, P = 0 0351) and the C allele (OR = 1.88, 95% CI = 1.02-3.46, P = 0 0416) of the rs731276 were significantly associated with increased risks of childhood ASD. None of the SNPs were associated with severity of childhood ASD. Our results reveal that certain polymorphisms in the VDR gene are a risk factor related to childhood ASD in the Han Chinese population.

Background: Both genetic and environmental factors play a role in the development of autism spectrum disorder (ASD). This case-control study examined the association between childhood ASD and single-nucleotide polymorphisms (SNPs) in genes involved with vitamin B12 and folate metabolism. Material/Methods: Genotypes of transcobalamin 2 (TCN2) rs1801198, methionine synthase (MTR) rs1805087, methionine synthase reductase (MTRR) rs1801394, and methylene tetrahydrofolate reductase (MTHFR) rs1801133 were examined in 201 children with ASD and 200 healthy controls from the Han Chinese population. Results: Our results showed no association of all examined SNPs with childhood ASD and its severity. Conclusions: None of the examined SNPs were a risk factor for the susceptibility to childhood ASD and severity of the disease in a Han Chinese population.

Previous studies have revealed that long noncoding RNA (lncRNA) and microRNA play a crucial role in autism, which is a childhood neurodevelopmental disorder with complicated genetic origins. Hence, the study concerns whether lncRNA C21orf121/bone morphogenetic proteins 2 (BMP2)/miR-140-5p gene network affects directed differentiation of stem cells from human exfoliated deciduous teeth (SHED) to neuronal cells in rats with autism. Autism models were successfully established. The neuron cells that differentiated from SHED cell were identified. The expression of lncRNA C21orf121, miR-140-5p, BMP2, Nestin, βIII-tubulin, and microtubule-associated protein 2 (MAP2) and the expression of neuron-specific enolase (NSE) were examined. Besides, the gap junction (GJ) function of SHED, the intracellular free Ca 2+ concentration, and the social behavior and repetitive stereotyped movements of rats in autism were detected. The target relationship between lncRNA C21orf121 and miR-140-5p and that between miR-140-5p and BMP2 were also verified. Firstly, we successfully isolated SHED and identified the differentiated neurons of SHED. Besides, the expression of BMP2, MAP2, Nestin, βIII-tubulin, NSE positive rate, GJ function, and intracellular free Ca 2+ concentration were increased with the upregulation of C21orf121 and downregulation of miR-140-5p, and accumulated time of repetitive stereotyped movements decreased and the frequency of social behavior increased. The results indicate that lncRNA C21orf121 as a competing endogenous RNA competes with BMP2 binding to miR-140-5p, thereby promoting SHED to differentiate into neuronal cells via upregulating BMP2 expression.

Genetic variants have been implicated in the development of autism spectrum disorder (ASD). Recent studies suggest that solute carriers (SLCs) may play a role in the etiology of ASD. This purpose of this study was to determine the association between single nucleotide polymorphisms (SNPs) in SLC19A1 and SLC25A12 genes with childhood ASD in a Chinese Han population. A total of 201 autistic children and 200 age- and gender-matched healthy controls were recruited. A TaqMan probe-based real-time PCR approach was used to determine genotypes of SNPs corresponding to rs1023159 and rs1051266 in SLC19A1, and rs2056202 and rs2292813 in SLC25A12. Our results showed that both the T/T genotype of rs1051266 (odds ratio (OR) = 1.85, 95% confidence interval (CI) = 1.06–3.23, P = 0.0301) and the T allele (OR = 1.77, 95% CI = 1.07–2.90, P = 0.0249) of rs2292813 were significantly associated with an increased risk of childhood ASD. In addition, the G-C haplotype of rs1023159-rs1051266 in SCL19A1 (OR = 0.71, 95% CI = 0.51–0.98, P = 0.0389) and C-C haplotype of rs2056202-rs2292813 in SLC25A12 (OR = 0.58, 95% CI = 0.35–0.96, P = 0.0325) were associated with decreased risks of childhood ASD. There was no significant association between genotypes and allele frequencies with the severity of the disease. Our study suggests that these genetic variants of SLC19A1 and SLC25A12 may be associated with risks for childhood ASD.

PURPOSE:Autism spectrum disorder (ASD) is a group of developmental brain disorders caused by genetic and environmental factors. The objective of this study was to investigate whether single nucleotide polymorphisms (SNPs) in genes related to immune function were associated with ASD in Chinese Han children.MATERIALS AND METHODS:A total of 201 children with ASD and 200 age- and gender-matched healthy controls were recruited from September 2012 to June 2106. A TaqMan probe-based approach was used to genotype SNPs corresponding to rs28532698 and rs4301112 in CD157, rs855867 in AIM2, and rs2237126 in JARID2. Case-control and case-only studies were performed to determine the contribution of SNPs to the predisposition of disease and its severity, respectively.RESULTS:Our results revealed that the genotypes and allele frequencies of these SNPs were not significantly associated with childhood ASD and its severity in this population.CONCLUSIONS:Results of our study suggest that these SNPs are not predictors of childhood ASD in the Chinese Han population. The discrepant results suggest the predictor roles of SNPs have to be determined in different ethnic populations due to genetic heterogeneity of ASD.

目的 探讨多巴脱羧酶(dopa decarboxylase,DDC)与多巴胺受体-1(dopamine receptor-1,DRD1)基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)和中国汉族儿童孤独症之间的关系.方法 应用TaqMan探针方法对97名孤独症患儿和100名健康儿童进行DDC基因rs6592961和DRD1基因rs251937单核苷酸多态性的基因型测定.用儿童孤独症评定量表(Children Autism Rating Scale,CARS)评价孤独症患儿临床表型特征.应用x2检验比较不同基因型和等位基因在孤独症病例组和对照组之间的分布情况.结果 ①病例组和对照组儿童的DDC基因rs6592961位点和DRD1基因rs251937位点等位基因频率和基因型分布上差异均无统计学意义(P＞0.05).②孤独症组病情轻中度与重度儿童DDC的rs6592961和DDR1的rs251937位点等位基因频率和基因型分布上差异均无统计学意义(P＞0.05).结论 DDC基因rs6592961位点和DRD1基因rs251937位点单核苷酸多态性可能与中国汉族儿童孤独症的发病无关联.

目的 分析萧山区变态反应性疾病儿童过敏原阳性率、主要过敏原种类,以针对性预防和治疗.方法 采用德国MEDIWISS Analytic GmbH公司产过敏原检测仪及过敏原诊断试剂盒检测321例儿童血清中总IGE及19种吸人性和食人性过敏原特异性IGE抗体.结果 疾病组儿童血清中总IGE阳性率为80.8％(173/214),特异性IGE抗体阳性率为61.2％(131/214).吸人性过敏原前三位分别为尘螨、屋尘、狗毛皮屑;食人性过敏原前三位分别为牛奶、鸡蛋白、牛肉.不同性别总IGE阳性率及特异性IGE抗体阳性率无显著差异性.＜3岁组以食人性过敏原为主,学龄期组以吸人性过敏原为主.变态反应性疾病组过敏原特异性IGE阳性中,一种过敏原阳性率、二种过敏原阳性率、三种及以上过敏原阳性率分别为31.8％(68/214)、27.6％(59/214)、21.5％(46/214).结论 变态反应性疾病儿童血清中总IGE和过敏原特异性IGE阳性率明显高,吸人性过敏原以尘螨为主,食人性过敏原以牛奶为主,三种及以上过敏原阳性率占21.5％(46/214).变态反应性疾病儿童在春秋二季尤其应避免接触过敏原.

The solute carrier family 25 (aspartate/glutamate carrier), member 12 gene (SLC25A12) has been strongly posed as a candidate gene for autism spectrum disorder (ASD) given its important role in mitochondrial function and adenosine triphosphate (ATP) synthesis. Evidence is mounting for the association between SLC25A12 variants (rs2056202 and rs2292813) and ASD risk, but the results are inconsistent. To clarify the effect of these two variants on ASD, a meta‐analysis integrating case‐control and transmission disequilibrium test (TDT) studies was performed. The PubMed, Embase, Cochrane Library, Web of Science, Chinese BioMedical Literature (CBM), Wanfang, and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched to identify relevant studies published up to May 2014. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to assess the strength of association. A total of 775 cases, 922 controls, and 1289 families available from 8 studies concerning rs2056202, and 465 cases, 450 controls, and 1516 families available from 7 studies concerning rs2292813 were finally included. In the overall meta‐analysis, the rs2056202 T allele and rs2292813 T allele were both significantly associated with a decreased risk of ASD (rs2056202: OR = 0.809, P = 0.001, 95%CI: 0.713–0.917, I2 = 0.0%, and Pheterogeneity = 0.526; rs2292813: OR = 0.752, P < 0.001, 95%CI: 0.649–0.871, I2 = 0.0%, Pheterogeneity = 0.486). Besides, subjects with T‐T haplotype of rs2056202–rs2292813 had a significantly reduced risk of ASD (OR = 0.672, P < 0.001, 95%CI: 0.564–0.801, I2 = 0.0%, Pheterogeneity = 0.631). Sensitivity analysis, cumulative meta‐analysis, and publication bias diagnostics confirmed the reliability and stability of our results. Our meta‐analysis suggests that rs2056202 and rs2292813 in SLC25A12 may contribute significantly to ASD risk. © 2015 Wiley Periodicals, Inc.

Objective To investigate the association between single nucleotide polymorphisms (SNPs) of DOPA decarboxylase (DDC) and dopamine receptor-1 (DRD1) and clinical phenotype feature in autistic children.Methods TaqMan probes real-time polymerase chain reaction (PCR) was used to determine genotype and allele of SNPs of DDC gene (rs6592961) and DRD1 (rs251937) gene in 97 autism children.The Children Autism Rating Scale (CARS) was used to evaluate clinical phenotype feature.Results There was no significant difference in the distribution of the allelic frequency and genotype between mild-medium group and severe group of CARS scores (P ＞ 0.05).For DDC gene (rs6592961),significant difference was found in subscale between genotypes G/G and A/A (P =0.043).For DRD1 gene (rs251937),significant difference was found in subscale between genotypes T/T and C/C (P =0.029).Conclusions In DDC gene (rs6592961),the children with G/G genotype were more obvious than the children with A/A genotype.In DRD1 gene (rs251937),the children with T/T genotype were more obvious than the children with C/C genotype.

Genetic factors play an important role in childhood autism. This study is to determine the association of single-nucleotide polymorphisms in dopa decarboxylase (DDC) and dopamine receptor-1 (DRD1) genes with childhood autism, in a Chinese Han population. A total of 211 autistic children and 250 age- and gender-matched healthy controls were recruited. The severity of disease was determined by Children Autism Rating Scale scores. TaqMan Probe by real-time polymerase chain reaction was used to determine genotypes and allele frequencies of single-nucleotide polymorphism rs6592961 in DDC and rs251937 in DRD1. Case-control and case-only studies were respectively performed, to determine the contribution of both single-nucleotide polymorphisms to the predisposition of disease and its severity. Our results showed that there was no significant association of the genotypes and allele frequencies of both single-nucleotide polymorphisms concerning childhood autism and its severity. More studies with larger samples are needed to corroborate their predicting roles.