Novel allelic variants in the human serotonin transporter gene linked polymorphism (5-HTTLPR) among depressed patients with suicide attempt.
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.
Segal
Jair
J
Universidade Federal do Rio Grande do Sul (UFRGS), Post-Graduate Program in Medical Sciences: Psychiatry, Brazil.
Schenkel
Laila Cigana
LC
Oliveira
Marcela Herbstrith de
MH
Salum
Giovanni Abrahão
GA
Bau
Claiton Henrique Dotto
CH
Manfro
Gisele Gus
GG
Leistner-Segal
Sandra
S
D000328:Adult; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D003866:Depressive Disorder / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013406:Suicide, Attempted / Q000523:psychology*
D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin