Polymorphisms of estrogen metabolism-related genes ESR1 , UGT2B17 , and UGT1A1 are not associated with osteoporosis in artificial menopausal Japanese women

Abstract

IntroductionBilateral salpingo-oophorectomy (BSO) is a risk factor for osteoporosis. Previous studies have reported an association between genetic polymorphisms and the risk of developing osteoporosis. However, the relationship between osteoporosis and genetic polymorphisms in Japanese women treated with BSO is not well understood. To improve the quality of life for post-BSO patients, it is important to determine the genetic factors that influence their risk for osteoporosis. The aim of this study was to investigate the association between gene variations of estrogen metabolism-related genes and osteoporosis in surgically menopausal patients, which may improve their quality of life.Material and methodsThis study included 203 menopausal women treated with BSO because of gynecologic disorders. One hundred and twenty-six women with artificial (surgical) menopause, who had undergone BSO in the premenopausal period, were compared with 77 women with natural menopause, who had undergone BSO in the postmenopausal period. The women were tested for bone mineral density to diagnose osteoporosis. Polymorphisms of estrogen receptor 1 (ESR1) and UDP-glucuronosyl transferase (UGT) genes UGT2B17 and UGT1A1 were analyzed, and their association with bone mass and osteoporosis was statistically evaluated.ResultsNo significant association was found between osteoporosis and polymorphisms in ESR1, UGT2B17, or UGT1A1 in both groups, suggesting that BSO might be a more significant physiological factor in influencing bone mass density compared to genetic variations.ConclusionsThese results suggest that the ESR1, UGT2B17, and UGT1A1 polymorphisms are not genetic factors affecting osteoporosis in postmenopausal Japanese women.

The importance of the UGT1A1 variants in the development of osteopenia and osteoporosis in postmenopausal women

“…Our findings regarding lack of an association between the UGT1A1*6 variant with osteoporosis are consistent with the observations made in the population of postmenopausal Japanese women. Yokota et al, also did not report a correlation between the UGT1A1 variant and osteoporosis 16 . Nevertheless, it should be taken into account that the absence of statistically significant differences between the compared groups may have resulted from the cross-sectional nature of the study.…”

“…UGT1A1 is involved in the process of estrogen conjugation and elimination 16 . In the present study, the frequency of the UGT1A1*28 variant among Caucasian women was assessed.…”

“…Low body weight is a predisposing factor for developing osteoporosis, although it remains debatable whether obesity can be a protective factor against bone mass loss 35 , although higher body weight in healthy controls may support the hypothesis. Moreover, taking into account the function of the UGT1A1 protein, one of the main proteins involved in glucuronidation of drugs and other compounds 14 , as well as elimination of estrogens and the consequent reduction of their circulating pool 16 , lower weight may be expected in women with osteoporosis as compared to their postmenopausal healthy peers. The observed values of body mass parameters may be related to the fact that an increase in body weight is accompanied by a corresponding increase in insulin resistance, which attempts to be compensated by elevated secretion of insulin, whose receptors are located on the surface of the osteoblasts.…”

“…UGT1A1 is expressed in the uterus and is involved in the conjugation and elimination of estrogens. Studies indicate that permanent estrogen deficiency after menopause is the main cause of osteoporosis in older women 16 . However, the relationship between osteoporosis and the UGT1A1 gene variant in Caucasian postmenopausal women remains to be fully elucidated.…”

UGT1A1 polymorphism as a prognostic indicator of stage I ovarian clear cell carcinoma patients treated with irinotecan

“…We examined UGT1A1*6 (211 G→A) and UGT1A1*28 ([TA] 6 TAA→[TA] 7 TAA) alleles as previously described (4,6). UGT1A1*1/*1 was defined as wild-type (normally functioning phenotype).…”