Mohammad Naushad Shaik, Jain Jamal Md Nurul, Chintakindi Krishna Prasad, Singh Ram Prakash, Naik Usha, Akella Radha Rama Devi
Center for DNA Fingerprinting and Diagnostics, Niloufer Hospital, Hyderabad, India.
Psychiatr Genet. 2009 Aug;19(4):171-6. doi: 10.1097/YPG.0b013e32832cebd2.
To investigate whether genetic polymorphisms are the underlying causes for aberrations in folate pathway that was reported in autistic children.
A total of 138 children diagnosed as autistic based on Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria and Autism Behavior Checklist scoring and 138 age and sex matched children who are nonautistic were tested for five genetic polymorphisms, that is, cytosolic serine hydroxyl methyl transferase (SHMT1 C1420T), methylene tetrahydrofolate reductase (MTHFR C677T and MTHFR A1298C), methionine synthase reductase (MTRR A66G), methionine synthase (MS A2756G) using PCR-restriction fragment length polymorphism methods. Fisher's exact test and logistic regression analysis were used for statistical analyses.
MTHFR 677T-allele frequency was found to be higher in autistic children compared with nonautistic children (16.3 vs. 6.5%) with 2.79-fold increased risk for autism [95% confidence interval (CI): 1.58-4.93]. The frequencies of MTRR 66A allele (12.7 vs. 21.0%) and SHMT 1420T allele (27.9 vs. 45.3%) were lower in autistic group compared with nonautistic group with odds ratios 0.55 (95% CI: 0.35-0.86) and 0.44 (95% CI: 0.31-0.62), respectively, indicating reduced risk. MTHFR 1298C-allele frequency was similar in both the groups (53.3 vs. 53.6%) and hence individually not associated with any risk. However, this allele was found to act additively in the presence of MTHFR 677T allele as evidenced by 8.11-fold (95% CI: 2.84-22.92) risk associated with MTHFR 677CT+TT/1298AC+CC genotypes cumulatively.
MTHFR C677T is a risk factor, whereas MTRR A66G and SHMT C1420T polymorphisms reduce risk for autism. MTHFR A1298C acts additively in increasing the risk for autism.
探讨基因多态性是否为自闭症儿童中报道的叶酸代谢途径异常的潜在原因。
根据《精神疾病诊断与统计手册》第四版标准及自闭症行为量表评分，共纳入138名被诊断为自闭症的儿童，以及138名年龄和性别匹配的非自闭症儿童，采用聚合酶链反应-限制性片段长度多态性方法检测5种基因多态性，即胞质丝氨酸羟甲基转移酶（SHMT1 C1420T）、亚甲基四氢叶酸还原酶（MTHFR C677T和MTHFR A1298C）、甲硫氨酸合成酶还原酶（MTRR A66G）、甲硫氨酸合成酶（MS A2756G）。采用Fisher精确检验和逻辑回归分析进行统计学分析。
发现自闭症儿童中MTHFR 677T等位基因频率高于非自闭症儿童（16.3%对6.5%），患自闭症的风险增加2.79倍[95%置信区间（CI）：1.58 - 4.93]。自闭症组中MTRR 66A等位基因频率（12.7%对21.0%）和SHMT 1420T等位基因频率（27.9%对45.3%）低于非自闭症组，优势比分别为0.55（95% CI：0.35 - 0.86）和0.44（95% CI：0.31 - 0.62），表明风险降低。两组中MTHFR 1298C等位基因频率相似（53.3%对53.6%），因此单独与任何风险均无关联。然而，发现该等位基因在存在MTHFR 677T等位基因时具有累加作用，MTHFR 677CT + TT/1298AC + CC基因型累积的风险为8.11倍（95% CI：2.84 - 22.92）。
MTHFR C677T是一个风险因素，而MTRR A66G和SHMT C1420T多态性降低自闭症风险。MTHFR A1298C在增加自闭症风险方面具有累加作用。
