Biomarkers in children with Autism: A case control Study
Sheffali Gulati, Chinthana L, Gautam Kamila, Thirumurthy Velpandian, Seema Kapoor, Vinod Scaria, Shobha Sharma, Kakali Purkayastha, Sanjeeda Khan, Prashant Jauhari, Biswaroop Chakrabarty, Prateek Kumar Panda, Sudip Kumar Datta, Pradeep Kumar Chaturvedi, R. M. Pandey
Objectives:Tocompare the levels of methylation pathway biomarkers, advanced glycation end-products and correlate with severity of autism (CARS score), sensory issues (SP2 score), co-morbidities (CBCL score) and DQ/IQ(MISIC/VSMS/BKT) Methods: Children with ASD between 2-18 years fulfilling DSM-5 criteria were selected. Subjects with chronic-illness or those on any antioxidant therapy/multivitamins/anti-epileptic drugs were excluded. Results: 100 cases (male-82) and 50controls (male-41) were enrolled.The frequency of CC,CT and TT genotypes in ASD group was 84%,14% and 2% and in control group was 86%,12% and 2% respectively; thus, C677T polymorphism was not associated with increased ASD risk. The median level of serum homocysteine in ASD group was 9 µmol/L(95% CI: 7-16 µmol/L), was significantly higher than controls 7 µmol/L(95% CI:4-11µmol/L)(p=0.01). The prevalence of hyper-homocystinemia (>15µmol/L) was 13.4% in ASD as compared to 3.8% in controls with a significant difference(p=0.04). No significant correlation was found between prevalence of hyper-homocysteinemia and severity of autism/DQ/presence or absence of sensory andbehavioural issues. Among AGEs only dityrosine was found to be significantly elevated in ASD group. No significant difference was found between the median levels of plasma cysteine or methionine, urine uric-acid to creatinine ratio, arterial lactate, serum vitamin E, vitamin B12 and folate. Conclusions: The MTHFR C677T polymorphism is neither a risk nor protective factor. The prevalence of hyperhomocysteinemia is significantly higher in ASD compared to controls and is independent of MTHFR polymorphism and vitamin B12/folate levels. The evidence for the role of increased oxidative stress is also strengthened by the increased dityrosine levels.
Keywords: Autism Spectrum Disorder, Biomarker
Sheffali Gulati
All India Institute of Medical Sciences
India
Chinthana L
All India Institute of Medical Sciences
India
Gautam Kamila
All India Institute of Medical Sciences
India
Thirumurthy Velpandian
All India Institute of Medical Sciences
India
Seema Kapoor
Maulana Azad Medical College
India
Vinod Scaria
Institute of Genomics and Integrutive
India
Shobha Sharma
All India Institute of Medical Sciences
India
Kakali Purkayastha
All India Institute of Medical Sciences
India
Objectives:Tocompare the levels of methylation pathway biomarkers, advanced glycation end-products and correlate with severity of autism (CARS score), sensory issues (SP2 score), co-morbidities (CBCL score) and DQ/IQ(MISIC/VSMS/BKT) Methods: Children with ASD between 2-18 years fulfilling DSM-5 criteria were selected. Subjects with chronic-illness or those on any antioxidant therapy/multivitamins/anti-epileptic drugs were excluded. Results: 100 cases (male-82) and 50controls (male-41) were enrolled.The frequency of CC,CT and TT genotypes in ASD group was 84%,14% and 2% and in control group was 86%,12% and 2% respectively; thus, C677T polymorphism was not associated with increased ASD risk. The median level of serum homocysteine in ASD group was 9 µmol/L(95% CI: 7-16 µmol/L), was significantly higher than controls 7 µmol/L(95% CI:4-11µmol/L)(p=0.01). The prevalence of hyper-homocystinemia (>15µmol/L) was 13.4% in ASD as compared to 3.8% in controls with a significant difference(p=0.04). No significant correlation was found between prevalence of hyper-homocysteinemia and severity of autism/DQ/presence or absence of sensory andbehavioural issues. Among AGEs only dityrosine was found to be significantly elevated in ASD group. No significant difference was found between the median levels of plasma cysteine or methionine, urine uric-acid to creatinine ratio, arterial lactate, serum vitamin E, vitamin B12 and folate. Conclusions: The MTHFR C677T polymorphism is neither a risk nor protective factor. The prevalence of hyperhomocysteinemia is significantly higher in ASD compared to controls and is independent of MTHFR polymorphism and vitamin B12/folate levels. The evidence for the role of increased oxidative stress is also strengthened by the increased dityrosine levels.
Keywords: Autism Spectrum Disorder, Biomarker
Sheffali Gulati
All India Institute of Medical Sciences
India
Chinthana L
All India Institute of Medical Sciences
India
Gautam Kamila
All India Institute of Medical Sciences
India
Thirumurthy Velpandian
All India Institute of Medical Sciences
India
Seema Kapoor
Maulana Azad Medical College
India
Vinod Scaria
Institute of Genomics and Integrutive
India
Shobha Sharma
All India Institute of Medical Sciences
India
Kakali Purkayastha
All India Institute of Medical Sciences
India
