The Role of Phosphatidylethanolamine N-Methyltransferase () and Its Waist-Hip-Ratio-Associated Locus rs4646404 in Obesity-Related Metabolic Traits and Liver Disease.

In previous genome-wide association studies (GWAS), genetic loci associated with obesity and impaired fat distribution (FD) have been identified. In the present study, we elucidated the role of the gene, including the waist-hip-ratio-associated single nucleotide polymorphism rs4646404, and its influence on obesity-related metabolic traits. DNA from 2926 metabolically well-characterized subjects was used for genotyping. expression was analyzed in paired visceral (vis) and subcutaneous (sc) adipose tissue (AT) from a subset of 574 individuals. Additionally, expression was examined in vis, sc AT and liver tissue in a separate cohort of 64 patients with morbid obesity and liver disease. An in vitro knockdown was conducted in murine epididymal and inguinal adipocytes. Our findings highlight tissue-specific variations in mRNA expression across the three studied tissues. Specifically, vis mRNA levels correlated significantly with T2D and were implicated in the progression of non-alcoholic steatohepatitis (NASH), in contrast to liver tissue, where no significant associations were found. Moreover, sc expression showed significant correlations with several anthropometric- and metabolic-related parameters. The rs4646404 was associated with vis AT expression and also with diabetes-related traits. Our in vitro experiments supported the influence of on adipogenesis, emphasizing its role in AT biology. In summary, our data suggest that plays a role in regulating FD and has implications in metabolic diseases.