We tested for association between the dichotomous clinical phenotype of alcohol dependence and seven single nucleotide polymorphisms (SNPs) in ZNF699 in our sample of 565 genetically independent cases and 496 siblings diagnosed with AD, and 609 controls.
Twenty-four of the differentially regulated genes were previously identified by genome-wide association studies of alcohol use disorders; this raises the potential interest of genes not normally associated with alcoholism, such as suppression of tumorigenicity 18 (ST18), BCL2-associated athanogene 3 (BAG3), and von Willebrand factor (VWF).
The gene coding for apolipoprotein E receptor 2 (APOER2) and the gene coding for ubiquitin-associated protein-2 (UBAP2) are among the most appropriate for follow-up in human and nonhuman species as contributors to risk for alcohol dependence.
For AD+DD, the risk regions centered on TTC12 exon 3 [optimal individual haplotype simulated p (p(oihs)) = 0.000015], and another extended from ANKK1 exon 8 to DRD2;C957T (p(oihs) = 0.0028), in both samples.
Apomorphine challenge tests measuring GH responses on 5 time points were performed on day 1 of alcohol detoxification in 43 patients with alcohol dependence; patients were genotyped for 11 polymorphisms including DRD2, ANKK1, NCAM1 and TTC12.
We conclude that risk for AD is attributable in part to variants in four regions within this cluster: exon 3 of TTC12, exon 12/intron13 of NCAM1 and exons 2 and 5 of ANKK1.
Various types of phenotypic markers are discussed and alcoholism is taken as a model for a more detailed discussion of available putative phenotypic markers and of research strategies to be used, namely the pharmacological challenge in high risk subjects (e.g. ethanol and TRH challenge).
The results of the TRH test and the DST point to similar endocrinological patterns in alcoholics as in depressive patients and thus support the hypothesis of a link between alcoholism and depression.
Polymorphisms in the promoter region may influence the function of the TPH1 gene and further influence the proclivity of alcohol dependence in one ethnic group in Taiwan.
A case group of males with type 2 alcoholism (N=59) and a control group of healthy males (N=282), both of Croatian origin, were analyzed for the frequency distribution of polymorphisms in 5HT transporter (5HTT-VNTR2, 5HTT-LPR), monoamine oxidase A (MAOA-uVNTR) and B (MAOB-A/G) and tryptophan hydroxylase 1 (TPH1 A218C) and 2 (TPH2 G-703T) genes.
The intron 7 variant in the TPH gene showed significant evidence for linkage to suicidality (P=.006 in unaffected sib pairs), severe suicide attempts (P=.006 in unaffected sib pairs; regression: P=.01), alcoholism (P=.003 in unaffected sib-pairs; regression: P=.02), and Karolinska Scales of Personality socialization score (regression: P=.002).
The genotype and allele frequencies of TPH1 were investigated in 182 male hospitalized patients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for alcohol dependence.
Overall, the RB1, p53 and Wnt pathways were commonly affected in HCCs of different etiology, probably reflecting common pathogenetic mechanisms, i.e., chronic liver injury and cirrhosis, but tumors associated with alcoholism had more frequent alterations in the RB1 and p53 pathways than those caused by HCV infection.
There was no correlation between expression of the p53 gene and age, sex, tobacco intake, alcoholism, and familiar history of cancer or clinical stage of the disease.
This study was undertaken to delineate whether transketolase abnormality (i.e., high Michaelis Menton constant (Km) for thiamine pyrophosphate), previously reported in patients with Wernicke-Korsakoff syndrome is prevalent among familial chronic alcoholic men and their sons without prior history of alcohol abuse but who are at high risk for alcoholism.
Gene level disturbances in cellular and molecular networks impacted by alcohol and alcoholism pathology include transketolase (TKT), transferrin (TF), and myelin (e.g., MBP, MOBP, and MOG).
Interestingly, several genes (TESK2, TIPARP, THEMIS, ABLIM1, RFX4, STON2 and LILRA1) are associated with three personality traits with p < 10(-3) using single trait analysis and AD.
The top hit of PKNOX2 (rs750338 with p=1.47 × 10(-6)) in the meta-analysis was replicated with the Australian Twin-Family Study of 778 families (p=1.39 × 10(-2)) Furthermore, several flanking SNPs of the top hits in the meta-analysis demonstrated borderline associations with alcohol dependence in the family sample (top SNPs were rs2269655, rs856613, and rs10496768 with p=4.58 × 10(-3), 2.1 × 10(-4), and 2.86 × 10(-3) for KIAA0040, NRD1 and THSD7B, respectively).
Interestingly, several genes (TESK2, TIPARP, THEMIS, ABLIM1, RFX4, STON2 and LILRA1) are associated with three personality traits with p < 10(-3) using single trait analysis and AD.