Kk. Kidd et al., DRD2 HAPLOTYPES CONTAINING THE TAQI A1 ALLELE - IMPLICATIONS FOR ALCOHOLISM RESEARCH, Alcoholism, clinical and experimental research, 20(4), 1996, pp. 697-705
In recent years, a possible role of the dopamine D-2 receptor (DRD2) l
ocus in the etiology of alcoholism has been the focus of considerable
attention. The literature now contains a mix of association studies wi
th positive and negative conclusions. Various methodological flaws und
ermine the claims in many of the studies that conclude a positive asso
ciation exists between alcoholism and the DRD2A1 allele at the Taql '
'A'' site. Although the studies with negative findings have more often
come from studies using better analytic methodology, satisfactory res
olution of whether or not genetic variation at the DRD2 locus plays so
me role in the etiology of alcoholism is unlikely to come from additio
nal studies of the kind conducted thus far; an approach enlightened by
a more thorough understanding of the population genetics of DRD2 and
the phylogenetic origins of the DRD2 alleles is one alternative. If ge
netic variation at the DRD2 locus affects susceptibility to alcoholism
, then such variation has a mutational and evolutionary history that c
an be traced with the aid of the various genetic polymorphisms that ha
ve been identified at the DRD2 locus. In this study, a third Taql rest
riction fragment-length polymorphism at DRD2, the Taql ''D'' site, has
been converted to polymerase chain reaction-based typing and its freq
uencies determined in 22 populations from around the world. Haplotypes
defined by the polymorphisms at the Taql ''B'' and ''A'' sites, and t
he short tandem repeat polymorphism in intron 2 have been constructed
and the diversity of haplotypes containing the DRD2A1 allele examined
for all 22 populations. The ancestral origins of the three Taql polym
orphisms have also been determined by sequencing the homologous region
s in other higher primates. Because A1-containing haplotypes in popula
tions of European, Middle Eastern, and African origin show considerabl
e diversity within and among populations, properly designed associatio
n studies in populations descended from those areas of the world need
to use haplotypes, not a singleallelic system, and need to use appropr
iate methods to compensate for the near impossibility of genetically m
atching unrelated control samples.