Alcoholism is a heritable disease that afflicts about 8% of the adult population. Its development and symptoms, such as craving, loss of control, physical dependence, and tolerance, have been linked to changes in mesolimbic, mesocortical neurotransmitter systems utilizing biogenic amines, GABA, and glutamate. Identification of genes predisposing to alcoholism, or to alcohol-related behaviors in animal models, has been elusive because of variable interactions of multiple genes with relatively small individual effect size and sensitivity of the predisposing genotype to lifestyle and environmental factors. Here, using near-isogenic advanced animal models with reduced genetic background interactions, we integrate gene mapping and gene mRNA expression data in segregating and congenic mice and identify glutamate receptor metabotropic 7 (Grm7) as a cis-regulated gene for alcohol consumption. Traditionally, the mesoaccumbal dopamine reward hypothesis of addiction and the role of the ionotropic glutamate receptors have been emphasized. Our results lend support to an emerging direction of research on the role of metabotropic glutamate receptors in alcoholism and drug addiction. These data suggest for the first time that Grm7 is a risk factor for alcohol drinking and a new target in addiction therapy.

Background: Polymorphisms of the gene encoding methylenetetrahydrofolate reductase (MTHFR) have been studied widely in various cancers, excluding thyroid cancer. However, reports on the association of various polymorphisms with certain cancers are contradictory. Materials and Methods: We have investigated whether the prevalence of the most common polymorphism (C677T) in the MTHFR gene has any link with various cancers, using genomic DNA and polymerase chain reaction restriction fragment length polymorphism (PCRRFLP) analysis. Results: The frequency of the heterozygous variant (677CT) but not that of 677TT was found to be significantly higher in colorectal cancer cases than in controls (p < 0.039; odds ratio 2.35 and 95% confidence interval 1.02–5.415). The frequencies for 677CT were 11.0 and 5.0% in colorectal cancer samples and controls, respectively. In ovarian cancer, the frequency of the 677TT variant was 6.0% which differed significantly (p < 0.026) from the control value of 1.0%. However, the frequencies of the variants in cervical, thyroid, and breast cancer cases did not differ from controls. Conclusions: Our data taken together with other reports indicates that the polymorphism C677T of MTHFR is a risk factor for developing colorectal cancer but not cervical, thyroid, and breast cancers. The present study also reconfirms that frequencies of the variants are not gender-specific.

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One strategy to identify neurochemical pathways of addiction is to map the relevant genes. In the present study we used 43 B6.C and 35 B6.I inbred RQI mouse strains, carrying <3% donor genome on C57BL/6ByJ background, for gene mapping. The strains were phenotyped for consumption of alcohol (12% v/v) in a two-bottle-choice paradigm, and genotyped for 396 microsatellite markers. The current mapping study extends our earlier experiment scanning five mouse chromosomes (1) to a whole-genome study, and discusses the differences and limitations. Data were analyzed with composite interval (CIM) and multiple interval (MIM) QTL mapping methods. CIM of B6.C strains detected significant QTLs on chrs. 6 and 12. A suggestive, but not significant, locus was detected in the B6.I strains on chr. 12. The best MIM model for B6.C strains confirmed one QTL on chr. 6 and one QTL on chr. 12., while the MIM model for the B6.I strains confirmed the suggestive locus on chr. 12. Some of the QTLs for alcohol consumption are new, while others confirm previously reported QTLs for alcohol preference, and alcohol acceptance.