A family-based study of Indian subjects from Kolkata reveals allelic association of the serotonin transporter intron-2 (STin2) polymorphism and attention-deficit-hyperactivity disorder (ADHD)
A family-based study of Indian subjects from Kolkata reveals allelic association of the serotonin transporter intron-2 (STin2) polymorphism and attention-deficit-hyperactivity disorder (ADHD)
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DOI：
10.1002/ajmg.b.30296
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发表时间：
2006-06-05
影响因子：
2.8
通讯作者：
Nandagopal, Krishnadas
中科院分区：
文献类型：
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作者：
Banerjee, Emili;Sinha, Swagata;Nandagopal, Krishnadas
5-羟色胺转运体（SLC 6A 4）多态性与注意力缺陷多动障碍（ADHD）的易感性有关，ADHD是一种高度遗传的异质性疾病，在儿童期发病。由于在印度没有这方面的调查，因此对来自加尔各答的56例ADHD病例和174例健康个体进行了SLC 6A 4启动子（5-HTTLPR）和内含子-2（STin 2）多态性的基因分型。我们报告说，观察到的等位基因频率的分布是一致的预期，按照哈代-温伯格平衡比例。包含5-HTTLPR和STin 2多态性系统的等位基因的成对组合表现出显著的（chi（2）= 14.74，df = 1; P = 0.0001）低幅度（D' = 0.269）的连锁不平衡。单倍型相对危险度（HHRR）（χ 2 = 4.92，P = 0.027; RR = 1.47; 95% CI = 1.01-2.13）和传递不平衡检验（TDT）（χ 2 = 7.00，P = 0.008; OR = 3.00; 95%CI = 1.53-5.90），表明STin2.12（A12）等位基因在ADHD病例中有显著的优先传递。A12等位基因的母系遗传在HHRR（chi（2）= 6.53，P = 0.011; RR = 2.00; 95% CI = 1.08-3.72）和TDT（chi（2）= 8-07，P = 0.005; OR = 6.50; 95%CI = 1.76-23.98），表明表观遗传机制在ADHD病因学中的新作用。类似的分析没有发现5-HTTLPR多态性与ADHD之间存在关联的证据。研究包括额外的多态性标记，多动症的主题和其他种族群体是必要的，以进一步证实目前的研究结果。(c)2006 Wiley-Liss，Inc.
Serotonin transporter (SLC6A4) polymorphisms are variously implicated in mediating susceptibility to attention-deficit-hyperactivity disorder (ADHD), a highly heritable and heterogeneous disorder with onset in childhood. Since there has been no survey in this regard from India, a sample of 56 ADHD cases and 174 healthy individuals from Kolkata were genotyped for the SLC6A4 promoter (5-HTTLPR) and intron-2 (STin2) polymorphisms. We report that the observed distribution of allele frequencies is consonant with that expected as per Hardy-Weinberg equilibrium proportions. Pair-wise combination of alleles comprising the 5-HTTLPR and STin2 polymorphic systems exhibit significant (chi(2) = 14.74, df = 1; P = 0.0001) linkage disequilibrium of low magnitude (D' = 0.269). The estimates of haplotype-based haplotype relative risk (HHRR) (chi(2) = 4.92, P = 0.027; RR = 1.47; 95% CI = 1.01-2.13) and transmission disequilibrium test (TDT) statistics (chi(2) = 7.00, P = 0.008; OR = 3.00; 95% CI = 1.53-5.90) using a family-based study design, indicate significant preferential transmission of the STin2.12 (A12) allele to ADHD cases. Maternal inheritance of the A12 allele is significant in terms of the HHRR (chi(2) = 6.53, P = 0.011; RR = 2.00; 95% CI = 1.08-3.72) and TDT (chi(2) = 8-07, P = 0.005; OR = 6.50; 95% CI = 1.76-23.98) suggesting a novel role for epigenetic mechanisms in the etiology of ADHD. Similar analyses yielded no evidence of association between the 5-HTTLPR polymorphism and ADHD. Studies including additional polymorphic markers, ADHD subjects and other ethnic groups are warranted to further substantiate the present findings. (c) 2006 Wiley-Liss, Inc.