In this study we investigated the possible involvement of the HTR2A gene in suicidal behavior by studying the A1438G polymorphism of this gene in 188 suicide attempters and 272 normal controls of Russian and Tatar descents. The genotype and allele frequency distribution of this polymorphism is presented in Table 1. ( Table 1 about here ) For A1438G polymorphism, genotype frequencies were in Hardy – Weinberg equilibrium in both cases and controls. The significant differences were found between cases and controls in the distribution of allele frequencies ( c­2 = 5.21, df = 1, p=0.028 ) and genotype frequencies on the reason of with higher G/G genotype frequency in the control group ( c­2 = 7.28, df = 2, p=0.021, OR=0.6, 95% CR=0.38 – 0.95 ).

Table 1. Genotype and allele frequency distribution of the A1438G polymorphism of the serotonin 2A receptor gene in the suicidal and control groups.

Conformity of genotype frequency to Hardy-Weinberg equilibrium.

Recently there were reports on association of the HTR2A gene (A1438G polymorphism) with schizophrenia [23], bipolar disorders[24, 25] and drug addiction [26]. Findings for suicidal behavior are controversy. Cao et al. (2001) reported that the genotype G/G was associated with male attempted suicides [27]. However, Geijer et al. (2000) found no association of the polymorphism with suicide attempts [28], such as Ono et al. (2001) – with completed suicide [29]. The conflicting findings concerning the association between the A1438G polymorphism and suicidality may due to various reasons. One of possible reasons is differences in genotype and allele freqency distributions between populations of different ethnic origins. The allele frequency of the A1438G polymorphism seems to be ethnic dependent. The frequency of the A allele is generally increased over the G allele in Japanese subjects [21, 29]. In contrast, the frequency of the G allele is higher than that of the A allele in Caucasians subject [30].

Table 2. Genotype and allele frequency distribution of the G861C polymorphism of the serotonin 1B receptor gene in the suicidal and control groups.

Conformity of genotype frequency to Hardy-Weinberg equilibrium.

When common group of healthy volunteers was divided for 2 subgroups – Russian and Tatar origins, we failed to find the significant differences in genotype ( c­2 = 3.85, df = 2, p=0.12 ) and allele ( c­2 = 1.61, df = 1, p=0.21 ) frequencies between these subgroups, such as in both subgroups of suicide attempters (of different ethnic origin) every genotype was shown to have almost equal frequencies.

However, our control subjects were significantly different from healthy controls of Japanese [3, 29] or French – Canadian [3] origins, but were not different from controls of mixed Caucasian origin [31] in the allele and genotype frequency distributions.

When genotype distributions in suicidal and control groups of Tatar ethnic origin were compared the G/G genotype frequency has seemed to be higher in the control group ( c­2 = 6.01, P = 0.015, df = 2, OR= 0.44, 95% CI= 0.22 – 0.86 ), at the same time the A allele was more frequent in the suicide attempters group ( c­2 = 4.65, df = 1, p = 0.025, OR= 1.54, 95% CI= 1.03 – 2.31 ). Between Russians cases and controls no significant differences in genotype and allele frequencies were found.

According to our data the allele A of the A1438G polymorphism of the HTR2A gene is associated with suicide attempts in the Tatars, but not in the Russians.

In the present study the possible involvement of the HTR1B gene in suicide is investigated. G861C polymorphism of this gene in 186 suicide attempters and 230 normal controls of Russian and Tatar descents is analyzed. The genotype and allele distribution of the G861C polymorphism is presented in the Table 2. (Table 2 about here) Genotype frequencies were in Hardy – Weinberg equilibrium in both control and suicidal groups. The G/G genotype was significantly more frequent in suicidal group in comparison with controls (OR= 1.9, 95% CI= 1.26 – 2.89). The allele G frequency in suicide attempters group was 0.71 VS 0.61 in controls (OR = 1.58, 95% CI= 1.17 – 2.14). So, significant differences were found between suicidal and control groups in genotype ( c­2 = 10.91, df = 2, p = 0.005) and allele frequencies ( c­2 = 9.39, df = 1, p = 0.003 ).

Our results showed that G861C polymorphism of the HTR1B gene was associated with suicide attempts. Our data is in agreement with the report of New et al. (2001) [10]. In contrast, our data in suicide attempters is in disagreement with the reports of Turecki et al. (2003) and Nishiguchi et al. (2001) that there was no association of this polymorphism with complete suicides, and also the report of Rujesku et al. (2003) of lack association with suicide attempts [18-20].

The possible reason of conflicting findings can be like above-mentioned one, namely, due to population differences in allele and genotype frequency distributions.

Among healthy volunteers significant differences were shown in genotype frequencies between Russians and Tatars ( χ² = 8.58, p = 0.011), connecting with increase of G/G genotype frequency in Russians: 0.60 vs 0.44. Both allele and genotype frequencies of the G861C polymorphism in our control group were significantly different from ones in control group of French-Canadian [17], Japanese [18], German [19] descent.

In Russian subgroup of suicide attempters the G/G genotype was significantly more frequent in comparison with Tatar suicidal subgroup: 0.59 vs 0.38 (χ² = 7.16, df = 1, p = 0.0083).

In Russian patients the G/G genotype (χ² = 14.76, df = 1, p = 0.0007, OR = 2.83, 95%CI = 1.63 - 4.91) and the allele G (χ² = 9.81, df = 1, p = 0.002, OR = 1.88, 95%CI = 1.24 - 2.84) were associated with suicidal behavior.

In Tatar subjects between controls and cases the significant differences were shown in the genotype frequencies (χ² = 6.45, df = 2, p = 0.04), on the reason of significantly higher frequency of the C/C genotype in the control group (χ² = 4.91, df = 1, p = 0.027, OR = 0.28, 95%CI = 0.09 - 0.89), but not in the allele frequency (χ² = 1.54, df = 1, p = 0.27).

According to our data the HTR1B gene is likely to be involved in the biological susceptibility to suicide. Both the genotype G/G and the allele G are rather can be markers of suicide attempts in Russian patients than in Tatar ones.