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ABSTRACT Chronic alcohol abuse and dependence are associated with dysfunctional dopaminergic neurotransmission in mesocorticolimbic circuits. Genetic and environmental factors have been shown to modulate susceptibility to alcohol dependence, and both may act through epigenetic mechanisms that can modulate gene expression, e.g. DNA methylation at CpG sites. Recent studies have suggested that DNA methylation patterns may change over time. However, few data are available concerning the rate of these changes in specific genes. A recent study found that hypermethylation of the promoter of the dopamine transporter ( DAT) gene was positively correlated with alcohol dependence and negatively correlated with alcohol craving. The aim of the present study was to replicate these findings in a larger sample of alcohol-dependent patients and population-based controls matched for age and sex. No difference in methylation level was observed between patients and controls, and no difference in methylation level was observed before and after alcohol withdrawal in patients. However, patients with more severe craving showed a trend towards lower DAT methylation levels ( P = 0.07), which is consistent with previous findings. Furthermore, in our overall sample, DAT methylation levels increased with age. Interestingly, a separate analysis of patients suggested that this finding was mainly driven by the patient group. Although the present data do not clarify whether chronic alcohol abuse is responsible for this phenomenon or merely enhances an ageing-specific process, our findings suggest that hypermethylation in alcohol-dependent patients is a consequence, rather than a cause, of the disorder. [ABSTRACT FROM AUTHOR]

In about half of the severe haemophilia A cases, the disease is caused by an inversion that split the F.VIII gene into two parts separated by ≈ 300–400 kb. Herein, we show that in the Turkish population this inversion mutation accounts for 29% of 141 haemophilia A cases and 42% of severe cases. Most of the inversions are of the distal type (72%) whereas nine were of the proximal type (28%). Haplotype analysis using 4 markers in the F.VIII gene did not reveal a single haplotype associated with the inversion. However, the pre- valence of one haplotype: HindIII (–) – Int13 (CA)20 – Int22 (CA + CT)26 – XbaI (–) is higher in the inversion patients. Since founder effect is excluded for the inversion patients, our results suggest that some as yet unknown factor(s) may make these alleles more prone for the inversion. However, a bias due to the low number of studied cases cannot be excluded. [ABSTRACT FROM AUTHOR]

Background: Long interspersed nuclear elements (LINE‐1) sequences constitute a substantial portion of the human genome, and their methylation often correlating with global genomic methylation. Previous studies have highlighted the feasibility of using LINE‐1 methylation to discriminate tumors from healthy tissues. However, most studies are based on only a few specific LINE‐1 CpG sites. Methods: Herein, we have performed a systematic fine‐scale analysis of methylation at 14 CpGs located in the 5′‐region of consensus LINE‐1, in bladder, colon, prostate, and gastric tumor tissues using a global degenerate approach. Results: Our results reveal variable methylation levels between different CpGs, as well as some tissue‐specific differences. Trends toward hypomethylation were observed in all tumors types to certain degrees, showing statistically significance in bladder and prostate tumors. Our data points toward the presence of unique LINE‐1 DNA methylation patterns for each tumor type and tissue, indicating that not the same CpGs will be informative for testing in all tumor types. Conclusion: This study provides an accurate guide that will help to design further assays that could avoid artifacts and explain the variability of obtained LINE‐1 methylation values between different studies. [ABSTRACT FROM AUTHOR]