No evidence for association of 5-HT2A receptor polymorphism with suicide

Letter to the Editor

No Evidence for Association of 5-HT2A ReceptorPolymorphism With Suicide

To the Editor:

In the February edition of this journal, Du et al.[2000] present a study on major depressive illness,comparing frequencies of the 102C/T polymorphism in5-HT2A receptor gene in control subjects, depressedpatients with suicidal ideation, and depressed patientswithout suicidal ideation. They observed a significantdifference in polymorphism frequency between the twopatient groups and suggest there is a significant asso-ciation between the 102C polymorphism in 5-HT2A re-ceptor gene and patients with suicidal ideation [Du etal., 2000]. In light of these findings, we investigatedwhether our sample group showed the same associa-tion. The sample comprised 68 completed suicides (in-dividuals with no significant organic disease for whomsuicide was the unequivocal cause of death) and 95controls (anonymous blood donors). Both groups camefrom the largely Caucasian South Australian popula-tion but were not otherwise matched.

Sample DNA was amplified in a 20 mL reaction mixusing the primers described by Du et al [2000]. Thecompleted PCR reaction was then halved, with half act-ing as an uncut control and the other 10 mL undergoingMsp1 digestion at 37°C for 3 hours. Samples, cut anduncut, were then electrophoresed on 3% agarose geland visualised by EtBr staining.

Chi-squared (x2) analysis was used to compare alleleand genotype frequencies between suicide and controlgroups in our study. Table I shows genotype distribu-tion and allele frequencies of the 102 T/C polymor-phism of the 5-HT2A receptor gene in our sample ofnormal controls and completed suicides as compared tocontrol subjects and depressed patients with suicidalideation reported by Du et al. [2000].

In this study, we did not observe a significant differ-ence in genotype frequencies or allelic distribution be-tween completed suicides and control subjects (x2 44.5, df 4 2, n.s. and x2 4 3.23, df 4 1, n.s.).

We acknowledge this comparison is limited by theabsence of specific diagnoses for our completed sui-

cides. However, a number of studies have estimatedthat two-thirds of those who suicide have major depres-sive disorders and as such we would have anticipatedthat the present results would have been more consis-tent with those of Du et al. [2000].

We are mindful that although it is reasonable to as-sume that suicidal ideation is a necessary precursor tosuicide, it is certainly not a sufficient explanation andthere are many other potential intervening variables.However, if in fact the 102C polymorphism were to beof significance in suicidal behaviour per se, indepen-dent of psychiatric diagnosis as suggested by Du et al.[2000], one would anticipate that it would be detectedmore readily in the present sample rather than that ofDu et al. [2000]. It should also be noted that othersinvestigating the relationship between variation at thislocus and suicide have reported a lack of association[Turecki et al., 1999].

Thus, although our findings cannot specifically re-fute the hypothesis of Du et al. [2000] that geneticvariation in the 5-HT2A receptor gene is associatedwith increased vulnerability to suicidal ideation inthose with major depression, they certainly do not sup-port the more important hypothesis that such a geneticvariation is associated with completed suicide itself.

ACKNOWLEDGMENTS

We thank the South Australian coroner, WayneChivell, for access to DNA samples from the completedsuicides; David Itzen for processing samples; and Shir-

*Correspondence to: Joanna Crawford, Department of Cytoge-netics and Molecular Genetics, Women’s and Children’s Hospital,North Adelaide, 5006, Australia

Received 29 March 2000; Accepted 18 July 2000

TABLE I. Genotype and Allele Frequencies of the 102 T/CPolymorphism of the 5-HT2A Receptor Gene

Subjects N

Genotypesa Allelesa

T/T T/C C/C T C

Controlsubjectsb 95 8 (8) 52 (55) 35 (37) 68 (36) 122 (64)

Completedsuicidesb 68 11 (16) 41 (60) 16 (24) 63 (46) 73 (54)

Controlsubjectsc 131 27 (21) 80 (61) 24 (18) 134 (51) 128 (49)

Suicidalideationc 78 11 (14) 35 (45) 32 (41) 57 (37) 99 (63)

aValues in parentheses represent percentage frequenciesbData from this study.cData from Du et al. (2000).

American Journal of Medical Genetics (Neuropsychiatric Genetics) 96:879–880 (2000)

© 2000 Wiley-Liss, Inc.

ley Richardson and Genevieve Secker for laboratoryassistance.

REFERENCES

Du L, Bakish D, Lapierre YD, Ravindran AV, Hrdina PD. 2000. Associa-tion of polymorphism of serotonin 2A receptor gene with suicidal ide-ation in major depressive disorder. Am J Med Genet (Neuropsychiatr.Genetics) 96:56–60.

Turecki G, Briere R, Dewar K, et al. 1999. Prediction of level of serotonin2A receptor binding by serotonin receptor 2A genetic variation in post-mortem brain samples from subjects who did or did not commit suicide.Am J Psychiatry 156:1456–1458.

Joanna Crawford*Grant R. SutherlandDepartment of Cytogenetics and

Molecular GeneticsWomen’s and Children’s HospitalNorth Adelaide, Australia

Robert D. GoldneyDepartment of PsychiatryUniversity of AdelaideAdelaide, Australia

880 Letter to the Editor