Segal Jair, Schenkel Laila Cigana, Oliveira Marcela Herbstrith de, Salum Giovanni Abrahão, Bau Claiton Henrique Dotto, Manfro Gisele Gus, Leistner-Segal Sandra
Universidade Federal do Rio Grande do Sul (UFRGS), Post-Graduate Program in Medical Sciences: Psychiatry, Brazil.
Neurosci Lett. 2009 Feb 13;451(1):79-82. doi: 10.1016/j.neulet.2008.12.015. Epub 2008 Dec 16.
A polymorphism in the serotonin transporter gene (5-HTTLPR) is being extensively studied for association with suicidal behavior. A new allelic variant within the 5-HTTLPR polymorphism was described but it has not been thoroughly analyzed in the recent literature. The SNP functional analysis demonstrated that the A variant of the L allele (L(A)) produces high levels of mRNA and that the G variant (L(G)) is equivalent to the S allele. Our aims were to compare the frequency of 5-HTTLPR alleles in 94 depressed patients who attempted suicide compared to 94 controls free of psychiatric disorder, including the embedded SNP rs25531. Using the biallelic classification, our sample contained 62 (33%) LL, 76 (40.4%) LS, and 50 (26.6%) SS individuals. Using the functional classification system, our sample contained 43 (22.5%) L'L', 84 (44.7%) L'S', and 61 (32.4%) S'S' individuals, with no significant differences between cases and controls in genotypic tests in either biallelic (chi(2)=2.543; df=2; p=0.280) and functional models (chi(2)=2.995; df=2; p=0.228). The minor allele frequency (MAF) - the S allele - did not show any distributional difference between cases and controls using biallelic classification system 0.51 vs. 0.43, (OR=1.41; CI95% 0.94 to 2.12; p=0.121). Also the S' allele of the functional classification system did not show any distributional difference between the two groups 0.59. vs. 0.51 (OR=1.35; CI95% 0.90 to 2.03; p=0.178). This study provided the possibility of a re-analysis of novell 5-HTTLPR functional variants identified within L allele that alters its mRNA production and thus changes its functionality. We could not find any association between both biallelic and functional 5-HTTLPR in depressed patients with suicide attempt, being the small sample size an important limitation for these results. In conclusion, we can suggest that despite the several studies in this issue, the exact effect and role of 5-HTTLPR in genetics of suicide is still unclear and should be better investigated for future studies.
血清素转运体基因（5-HTTLPR）中的一种多态性正被广泛研究与自杀行为的关联。5-HTTLPR多态性内的一种新的等位基因变体已被描述，但在最近的文献中尚未得到充分分析。单核苷酸多态性（SNP）功能分析表明，L等位基因的A变体（L(A)）产生高水平的信使核糖核酸（mRNA），而G变体（L(G)）等同于S等位基因。我们的目的是比较94名有自杀未遂行为的抑郁症患者与94名无精神疾病的对照者中5-HTTLPR等位基因的频率，包括内含的SNP rs25531。采用双等位基因分类，我们的样本中有62名（33%）LL、76名（40.4%）LS和50名（26.6%）SS个体。采用功能分类系统，我们的样本中有43名（22.5%）L'L'、84名（44.7%）L'S'和61名（32.4%）S'S'个体，在双等位基因（卡方=2.543；自由度=2；p=0.280）和功能模型（卡方=2.995；自由度=2；p=0.228）的基因型检测中，病例组和对照组之间均无显著差异。使用双等位基因分类系统，次要等位基因频率（MAF）——S等位基因——在病例组和对照组之间未显示出任何分布差异，分别为0.51对0.43，（比值比=1.41；95%置信区间0.94至2.12；p=0.121）。功能分类系统的S'等位基因在两组之间也未显示出任何分布差异，分别为0.59对0.51（比值比=1.35；95%置信区间0.90至2.03；p=0.178）。本研究提供了对在L等位基因内鉴定出的新型5-HTTLPR功能变体进行重新分析的可能性，该变体改变了其mRNA产生，从而改变了其功能。我们在有自杀未遂行为的抑郁症患者中未发现双等位基因和功能性5-HTTLPR之间存在任何关联，样本量小是这些结果的一个重要限制因素。总之，我们可以认为，尽管在这个问题上有多项研究，但5-HTTLPR在自杀遗传学中的确切作用和影响仍不清楚，未来研究应更好地对此进行调查。
