Polymorphisms in CYP17, COMT, and ESR1 genes in women after menopause and association with bone mineral density

Abstract

ABSTRACT. In this study, we evaluated genetic factors related to the mineral density during post-menopause. We evaluated 110 women in the first 5 years post-menopause, without previous hormone replacement therapy. Cytochrome P450 17 (CYP17) (rs743572), catechol-O-methyl transferase (COMT) (rs4680), and estrogen receptor 1 (ESR1) (rs9322331) were examined for the presence of polymorphisms. Clinical data were collected by anamnesis; all patients had the osseous densitometry examined using a lunar instrument to determine mineral osseous densitometry in the lumbar column (L2-L4). CYP17, COMT, and ESR1 genotyping was carried out by polymerase chain reaction with DNA collected from buccal swabs. The average age was 51.96 years. The average weights of the patients in control and osteopenia groups were 70.25 ± 12.00 and 62.45 ± 11.64, respectively (P = 0.001) and body mass index (P = 0.006; control: 29.43 ± 5.25; osteopenia: 26.72 ± 4.57). Related to CYP17 polymorphisms, 28.18% of women were TT (wild-type homozygous), 60% 15802-15810 (2015) were TC (heterozygous), and 11.82% were CC (mutated homozygous). Related to COMT polymorphisms, 53.64% of women were GG (wild-type homozygous), 37.27% were GA (heterozygous), and 9.09% were AA (mutated homozygous). Related to ESR1, 53.64% of women were CC (wildtype homozygous), 40.91% were CT (heterozygous), and 5.45% were TT (mutated homozygous). The ESR1 variant allele was significantly higher in the osteopenia group when compared with women in the normal group (P = 0.02). ESR1 may be associated with low mineral osseous densitometry, while CYP17 and COMT gene polymorphisms were not associated with mineral osseous densitometry.

Investigation of transcriptome mechanism associated with osteoporosis explored by microarray analysis

“…It is shown that CCAAT/enhancer-binding protein β (CEBPB), a TF, reduced bone mass in knockout mice (27). It has been found that estrogen receptor α (ESR1) is associated with low mineral osseous densitometry in women after menopause (28). Schmidt et al have shown that Sox8-deficient mouse exhibit a severely impaired bone formation, which is modulated by a strongly reduced expression of runt-related TF 2 (29).…”

The significance of polymorphism and expression of oestrogen metabolism-related genes in Chinese women with premature ovarian insufficiency

“…A polymorphism (rs743572) of CYP17 in the 5'-untranslated promoter region causes the replacement of a thymidine (T) with a cytosine (C) which is located 34 bp upstream of the translation initiation site. This polymorphism (rs743572) creates a potential Sp1-like (CCACC box) binding site that may be associated with higher oestrogen and androgen levels by increasing CYP17 gene expression and androgen biosynthesis (Gonçalves et al, 2015). The single nucleotide polymorphisms (SNPs) of the CYP17 T-34C are associated with several diseases of different races, including breast cancer, Cushing's syndrome and prostate cancer (Wang et al, 2011).…”

Efficacy and effects of transdermal hormone therapy in postmenopausal women

“…These symptoms may include undesirable hot flashes, breast tenderness migraines [3], and sleep disturbance [4]. The decrease in estrogen level is also associated with loss of bone mass [5] and adverse effects on lipid metabolism [6]. Hormone therapy (HT), which consists of estrogen and progestogen administration [7], is the most effective treatment to counteract menopause-related symptoms [4,8,9].…”