| Summary: | The <i>APOE</i> gene polymorphism is associated with the risk of the development of several neurological disorders. The aim of the study was to investigate the association of the <i>APOE</i> gene polymorphism with depression in the white adult population aged 25–64 years in Novosibirsk (Western Siberia). The third screening of the WHO program “MONICA-psychosocial” was conducted in 1994–1995. In total, 403 men (the average age was 34 ± 0.4 years, the response was 71%) and 531 women (the average age was 35 ± 0.4 years, the response was 72%) of the open population of residents aged 25–64 years of the Oktyabrsky district of Novosibirsk were examined. The “MONICA-MOPSY” psychosocial questionnaire was used to assess depression. A high level of depression was found in 12.8% of the population: in 8.9% of men and in 15.8% of women. The frequencies of <i>APOE</i> gene polymorphism genotypes ε2/3, ε2/4, ε3/3, ε3/4, and ε4/4 were 14.9%, 3.1%, 61.6%, 17.5%, and 2.9%, respectively. Carrying the ε3/4 genotype of the <i>APOE</i> gene increased the odds of developing major depression by 2.167 times (95% CI 1.100–4.266) compared to carrying the ε3/3 genotype of the <i>APOE</i> gene in people without depression (χ<sup>2</sup> = 5.120 df = 1 <i>p</i> = 0.024). Carriers of the ε4 allele were 2.089 times (95% CI 1.160–3.761) more likely to have a high level of depression than those without this allele and no depression (χ<sup>2</sup> = 6.148 df = 1 <i>p</i> = 0.013), and 2.049 times (95% CI 1.117–3.758) more likely to have a moderate level of depression than those without this allele (χ<sup>2</sup> = 5.470 df = 1 <i>p</i> < 0.019). The ε4 allele of the <i>APOE</i> gene is associated with a high level of depression.
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