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Evolution of the DRD2 gene haplotype and its association with alcoholism in Mexican Americans
- Source :
- Alcohol. 36:117-125
- Publication Year :
- 2005
- Publisher :
- Elsevier BV, 2005.
-
Abstract
- The human D2 dopamine receptor gene (DRD2) plays a central role in the neuromodulation of appetitive behaviors and is implicated in having a possible role in susceptibility to alcoholism. We genotyped an SNP in DRD2 Exon 8 in 251 nonalcoholic, unrelated, healthy controls and 200 alcoholic Mexican Americans. The DRD2 haplotypes were analyzed using the Exon 8 genotype in combination with five other SNP genotypes, which were obtained from our previous study. The ancestral origins of the DRD2 polymorphisms have been determined by sequencing the homologous region in other higher primates. Twenty DRD2 haplotypes, defined as H1 to H20 based on their frequency from high to low, were obtained in this major minority population. The ancestral haplotype "I-B2-G-C-G-A1" and two one-step mutation haplotypes were absent in our study population. The haplotype H1, "I-B1-T-C-A-A1", with the highest frequency in the population, is a three-step mutation from the ancestral form. The first five or eight major haplotypes make up 87% or 95% of the entire population, respectively. The prevalence of the haplotype H1+ (H1/H1 and H1/Hn genotypes) is significantly higher in alcoholics and alcoholic subgroups, including early onset drinkers and benders, than in their respective control groups. The Promoter -141C allele is in linkage disequilibrium (LD) with five other loci in the nonalcoholic group, but not in the alcoholic group. All of the other five loci are in LD in both the alcoholic and control groups. The DRD2 TaqI B allele is in complete LD with the allele located in intron 6. Five SNPs, Promoter -141C, TaqI B (or Intron 6), Exon 7, Exon 8, and TaqI A, are sufficient to define the DRD2 haplotypes in Mexican Americans. Our data indicate that the DRD2 haplotypes are associated with alcoholism in Mexican Americans.
- Subjects :
- Adult
Male
Primates
Linkage disequilibrium
Health (social science)
Genotype
TaqI
Population
Single-nucleotide polymorphism
Biology
Toxicology
Polymorphism, Single Nucleotide
Biochemistry
Linkage Disequilibrium
Behavioral Neuroscience
chemistry.chemical_compound
Gene Frequency
Mexican Americans
Animals
Humans
Allele
education
Allele frequency
Alleles
Aged
Genetics
education.field_of_study
Polymorphism, Genetic
Receptors, Dopamine D2
Haplotype
DNA
General Medicine
Middle Aged
Biological Evolution
Alcoholism
Haplotypes
Neurology
chemistry
Population study
Female
Subjects
Details
- ISSN :
- 07418329
- Volume :
- 36
- Database :
- OpenAIRE
- Journal :
- Alcohol
- Accession number :
- edsair.doi.dedup.....72b1234727e2ccb160b7abdb0ecbe495