Table 3.
Methylation levels of three prodynorphin methylation-associated SNPs associated with alcohol dependence in the dl-PFC of controls and alcoholics. Analysis of postmortem human brain specimens.
| ID | Genotype | SNP location | Number of subjects
|
Methylation levels %
|
P values | ||
|---|---|---|---|---|---|---|---|
| Controls | Alcoholics | Controls (Mean ± SD) | Alcoholics (Mean ± SD) | ||||
| rs1997794 | CC + CT | Promoter | 10 | 10 | 15.0 ± 10.0 | 23.0 ± 11.0 | 0.11c |
| rs6045819 | CC + CT | Exon 4 | 3 | 2 | 79.0 ± 13.0 | 66.0 ± 4.0 | |
| rs2235749 | CC + CT a, b | 3′-UTR | 10b | 12 | 60.9 ± 3.0 | 66.7 ± 3.9 | 0.001 |
| CC | 5 | 8 | 61.4 ± 2.1 | 65.5 ± 3.4 | <0.05 | ||
| CT | 5b | 4 | 60.4 ± 3.9 | 69.0 ± 4.0 | <0.02 | ||
Two-way analysis of variance with alcoholism and brain area (dl-PFC and MC) as factors, followed by post hoc Student’s t-test was used to evaluate differences between methylation levels of the 3′-UTR SNP (rs2235749; CC and CT genotypes were pooled) between control and alcoholics. A significant group effect [F(1.40) = 4.7, P < 0.05], a significant region effect [F(1.40) = 7.2, P = 0.01] and a significant group × region interaction [F(1.40) = 10.56, P < 0.01] were identified. Analysis of covariance failed to reveal significant influence of age, postmortem index, brain pH, agonal factor score, smoking history or storage time on the methylation differences. Data for the MC are shown in Table S5.
A statistical outlier (CT genotype, controls, dl-PFC) with methylation level exceeding two SDs from the mean value in the group was excluded from the analysis.
Student’s t-test was used for comparison. dl-PFC = dorsolateral prefrontal cortex; MC = ••; SD = standard deviation; SNP = single-nucleotide polymorphisms