5-羟色胺转运体基因多态与共患学习困难的儿童注意缺陷多动障碍的相关性

目的探讨共患学习困难(LD)的注意缺陷多动障碍(ADHD)患儿与5-羟色胺转运体(5-HTT)基因连锁多态区(5-HTTLPR)和第2内含子17 bp数目可变的顺向重复(stin2.VNTR)的关联关系。方法对126例共患LD的ADHD患儿和198例不共患LD的ADHD患儿的5-HTTLPR和stin2.VNTR两种多态进行检测,并采用传递不平衡检测(TDT)和单体型分析方法进行关联分析。结果(1)TDT检测:5-HTTLPR多态的S等位基因在共患LD的ADHD和ADHD混合型(ADHD-C)核心家系中优先传递(X2=5.831和5.281,P=0.015和0.020);所有家系均未观察到stin2.VNTR多态中的任何等位基因有传递不平衡现象(均P>0.05);(2)单体型分析:5-HTT基因与共患LD的ADHD和ADHD-C相关联(X2=11.391和13.343,v=3,P=0.010和P=0.004);单体型L／12在共患LD的ADHD和ADHD-C核心家系中传递较少(X2=10.317和8.948,v=1,P=0.001和0.003),而单体型L／10在共患LD的ADHD核心家系中传递较多(X2=4.065,v=1,P=0.044)。结论5-HTT基因可能与共患LD的ADHD相关联,其中主要为共患LD的ADHD-C亚型。

Association between serotonin transporter gene polymorphisms and attention deficit hyperactivity disorder with or without concomitant learning disorder

Objective To investigate the relationship between two serotonin transporter (5-HTT) gene polymorphisms, i. e. , 5-HTT linkage polymorphism region (5-HTTLPR) and 17 bp varied number tandem repeat ( Stin2. VNTR) polymorphisms, and attention deficit hyperactivity disorder ( ADHD) comorbid or not comorbid learning disorder (LD). Methods Blood samples were taken from 126 trios with probands of ADHD comorbid LD and 198 trios with probands of ADHD not comorbid LD. DNA was extracted and Polymerase chain reaction ( PCR) was performed to amplify the fragments of 5-HTTLPR and Stin2. VNTR polymorphisms. Transmit/disequilibrium test (TDT) and haplotype analysis were used to test the association of the two polymorphisms of 5-HTT gene and ADHD comorbid or not comorbid LD. Results (1) TDT analysis: revealed that S allele of 5-HTTLPR polymorphism was overtransmitted to probands of ADHD comorbid LD (X2 = 5.831, P= 0.015) and ADHD-C comorbid LD (X2=5.281, P=0.020), no allele of the Stin2. VNTR polymorphism was biased transmitted to probands of ADHD comorbid or not comorbid LD. (2) Haplotype analysis: The global haplotype analysis revealed that haplotype block composed by 5-HTTLPR and Stin2. VNTR polymorphisms was related to ADHD(X2 = 11. 391, v =3, P = 0.010) or ADHD-C (X2 = 13. 343, v =3, P =0.004) comorbid LD; the individual haplotype analysis revealed that the haplotype of L/12 was significantly untransmitted to probands with ADHD comorbid LD (X2 =10.317,v =1, P=0.001) and ADHD-C (X2 =8.948, v =1, P=0.003) comorbid LD, while the haplotype of L/10 was preferentially transmitted to probands with ADHD comorbid LD ( X2 =4. 065, v = 1, P =0. 044) ,but not to any subtypes of ADHD comorbid LD. Conclusion The 5-HTT gene may be related to ADHD comorbid LD, especially ADHD-C comorbid LD.