Linkage disequilibrium and haplotype analysis between serotonin receptor 1B gene variations and subtypes of alcoholism

A number of studies have reported a possible association between serotonergic pathway genes and alcoholism. A silent polymorphism (G to C substitution) in the gene encoding the autoreceptor 5-HT1B was linked to antisocial alcoholism in Finnish and an American Indian populations [Lappalainen et al., 1998: Arch Gen Psychiatry 55:989-994]. Several other polymorphisms of this gene have been investigated for their association with neuropsychiatric disorders. In the present study, a sample of 133 alcoholics without and 39 alcoholics with medical complications, and 88 normal controls was screened for three single nucleotide polymorphisms (SNPs), G861C, G261T, and C129T, in the 5-HT1B gene. The goal was to investigate their association with the disease, to measure the strength of linkage disequilibrium (LD) between the SNPs, and to compare haplotype frequencies between alcoholic groups and normal controls. Data was also analyzed on the basis of Type I (n = 47) and Type II (n = 85) alcoholism. There was no significant difference in the allele frequencies or the genotype distribution between any alcoholic groups, alcoholic subgroups, and controls for any polymorphism. G861C and C129T polymorphisms were in complete LD. The pattern of distribution of haplotypes was similar in patients and controls. It is concluded that these SNPs are not playing any direct role in the development of susceptibility to alcoholism in our patient sample.