BLOOD LIPID SPECTRUM, HOMOCYSTEIN, FOLIC ACID LEVELS AND GENES INVOLVED IN FOLATE METABOLISMIN WOMEN WITH POLYCYSTIC OVARY SYNDROME

Abstract

Dyslipidemia is one of the most common metabolic disorders associated with polycystic ovary syndrome (PCOS). Under the conditions of PCOS, DNA methylation disorders occur in most areas of genes involved in lipid metabolism. The development of dyslipidemia is also facilitated by an increase in the level of homocysteine (Hcy). The level of Hcy and DNA methylation are related to the state of the folate metabolism, which, in turn, depends on the sufficient amount of folic acid (FA), the activity of the enzymes 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR).

The aim. To study the blood lipid spectrum and its relationship with the levels of homocysteine, folic acid and polymorphism of MTHFR, MTR, MTRR gene in women with PCOS.

Material and methods. 159 women aged 20-28 years old were examined, who were divided into groups: the main one – 98 patients with the mutation variants of genes; comparison – 30 patients without studied genetic polymorphism; control – 31 healthy women without reproductive disorders. We investigated: Hcy, FA, total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C). A molecular genetic testing was conducted to identify the MTHFR, MTR and MTRR genes.

Results. Among PCOS patients with mutations genes, a higher frequency of hypercholesterolemia was observed 52.0% versus 26.6% (χ²=4,97; Р=0,026), increased TG level 47.9% versus 23.3% (χ²=4,75; Р=0,030) and a reduced HDL-C concentration of 51.0% versus 20.0% (χ²=7,77; Р=0,006). Carriers of C677T and T677T MTHFR mutation genes had significantly higher levels of cholesterol (P<0.001), TG (P<0.001), LDL-C (P<0.001) and lower HDL-C (P<0.05) compared to C677C, and the degree of expressiveness of the changes was more significant under the conditions of the homozygous T677T variant. Mutations in the MTHFR A1298C gene were associated only with a decrease in HDL-C concentration. We were not found probable discrepancies in the levels of cholesterol, TG, HDL-С, LDL-С at polymorphism of the MTR, MTRR genes. At 64.8% patients with PCOS an increase in the concentration of Hcy was revealed; frequency of increased concentration of Hcy (70,4% vs. 46,6%; χ²=4,69; Р=0,031) and its average level were higher at patients who had mutation genes then patients without genetic mutations. The carriers of mutational variants of the MTHFR gene showed a high risk of increased concentration of Hcy and correlations between its level and levels of cholesterol, TG, HDL-С. Mutational variants of genes were accompanied by a higher frequency of FA deficiency and the correlation between FA and Hcy, TG, HDL-C, which indirectly indicates the existence of a connection between FA status and blood lipid spectrum.

Conclusions. Polymorphism of MTHFR gene, increased level of homocysteine and deficiency of folic acid are factors of risk for the development of dyslipidemia in young patients with polycystic ovary syndrome.