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Dr. Turecki and Colleagues Reply

To the Editor: Drs. Hrdina and Du report the results they observed in a study (unpublished) in which they attempted to replicate our findings. In observing 17 depressed suicide subjects and 35 comparison subjects, they failed to find a relationship between variation at the T102C 5-HTR_2A polymorphism and 5-HTR_2A binding. As previously discussed (1), a possible explanation for this inconsistency may be related to the characteristics of the subjects included in our study, who were of French Canadian descent. This is a relatively young and isolated population that has a large background linkage disequilibrium (2). Thus, it is possible that a functional genetic variant located in a different coding or regulatory region of the 5-HTR_2A gene, rather than the T102C silent polymorphism, may in fact be responsible for our positive results.

This may not have been the case in the study by Drs. Hrdina and Du because they investigated subjects of Hungarian origin. Although they did not provide details about the specific ethnic composition of their study group, the Hungarian general population is composed of several different ethnic groups with admixture among most of them. The population is not known to have undergone any event leading to the presence of the relatively large linkage disequilibrium that may be observed in subjects chosen at random (3, 4).

An additional point relates to ascertainment differences between the studies. Drs. Hrdina and Du have focused their attention on depressed suicide victims (Du et al., 1999). Our findings are not related to the phenotype, but rather to a relationship between genetic variation and 5-HTR_2A binding. However, if there is less variation among binding levels in depressed patients, this group may have lower power to detect a positive association.

References

1. Turecki G, Brière R, Dewar K, Lesage A, Séguin M, Chawky N, Vanier C, Alda M, Joober R, Benkelfat C, Rouleau GA: Dr. Turecki and colleagues reply. Am J Psychiatry 2000; 157:1710–1711
2. Brais B, Bouchard JP, Xie YG, Rochefort DL, Chretien N, Tome FM, Lafreniere RG, Rommens JM, Uyama E, Nohira O, Blumen S, Korczyn AD, Heutink P, Mathieu J, Duranceau A, Codere F, Fardeau M, Rouleau GA: Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy. Nat Genet 1998; 18:164–167; erratum, 19:404[CrossRef][Medline]
3. Goedde HW, Benkmann HG, Kriese L, Bogdanski P, Czeizel A, Beres J: Genetic markers among three population groups of Hungary. Gene Geogr 1987; 1:109–120[Medline]
4. Guglielmino CR, Beres J: Genetic structure in relation to the history of Hungarian ethnic groups. Hum Biol 1996; 68:335–355[Medline]

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