Suwannee Chanprasertyothin

Serum oestradiol and oestrogen‐receptor gene polymorphism are associated with bone mineral density independently of serum testosterone in normal males

The physiological effects of oestrogens on bone in men were largely unanticipated until recently, when oestrogen deficiency in males with aromatase deficiency and oestrogen resistance was found to cause osteoporosis and delayed fusion of epiphyses despite sufficient serum testosterone. This raises the possibility that in normal men oestrogens rather than androgens are of physiological importance in bone maturation. In the present study, we examined the association of serum oestradiol (E2) compared to that of free testosterone (FT) with bone mineral density (BMD) in normal men. The effect of oestrogen receptor (ER) gene polymorphism on BMD in men was also addressed.

Oestrogen-receptor-α gene polymorphism affects response in bone mineral density to oestrogen in post-menopausal women

An oestrogen‐receptor‐α (ERα) gene polymorphism has been variably reported to be related to bone mass. To investigate whether this ERα gene polymorphism is associated with a functional difference, we assessed the response in bone mineral density (BMD) to oestrogen therapy in post‐menopausal women in relation to ERα gene polymorphism.

Estrogen receptor gene polymorphism is associated with bone mineral density in premenopausal women but not in postmenopausal women

In the present study, we examined the genotypes distribution of Pvu II estrogen receptor (ER) gene polymorphism and its association to bone mass in Thai females. Subjects consisted of 134 Thai females 54 of whom were premenopausal and 80 were postmenopausal. Pvu II ER gene polymorphism was determined by PCR-RFLP. Capital P represents the absence of the restriction site while small p indicates the presence of the restriction site. Forty nine (36.6%) of the subjects had pp genotype, while 59 (44.0%) had Pp genotype and 26 (19.4%) had PP genotype. There was no significant difference in age, body weight, height and calcium intake in premenopausal women with different genotypes. The results including years since menopause were similar in postmenopausal women. When including ER gene genotypes, age, body weight, height and dietary calcium intake in a stepwise multiple regression model, it was found that besides body weight ER gene polymorphism was associated with bone mineral density (BMD) at AP spine (p<0.05), lateral spine (p<0.05) femoral neck (p<0.05) and femoral trochanter (p<0.05) with the pp genotype having the least BMD. ER gene polymorphism was the only factor associated with BMD at Ward’s triangle, (p<0.05) while only body weight was associated with BMD at distal and mid radius. There was no difference in serum intact osteocalcin (OC) concentrations among subjects with different genotypes. ER gene polymorphism was not related to BMD in postmenopausal women at any skeletal site. Similarly, serum intact OC levels were not different among postmenopausal women with different genotypes. We concluded that Pvu II estrogen receptor gene polymorphism is associated with bone mineral density in premenopausal women but not in postmenopausal women. Estrogen receptor gene polymorphism may have a modulatory role in calcium and bone metabolism during adolescence and young adulthood.

The effects of oestrogen exposure on bone mass in male to female transsexuals

The importance of oestrogen on bone mineral density (BMD) in males was suggested by reports of patients with oestrogen resistance and aromatase deficiency who demonstrated osteoporosis and epiphyseal plate maturation defect despite high testosterone levels. In the present study, we examined the effects of oestrogen exposure on BMD in transsexual men.

Prevalence of the metabolic syndrome in Asian women with polycystic ovary syndrome: Using the International Diabetes Federation criteria

Background. Since insulin resistance and compensatory hyperinsulinemia are the major causes of the metabolic syndrome (MS) and are also the main pathophysiology of polycystic ovary syndrome (PCOS), PCOS women are at risk of MS. The aim of the present cross-sectional study was to determine the prevalence of MS in Asian women with PCOS using the International Diabetes Federation (IDF) criteria and to define the risk factors. Methods. One hundred and seventy women with PCOS were enrolled in the study from September 3, 2002 to June 14, 2005. A 75-g oral glucose tolerance test with plasma glucose and serum insulin levels was performed. Also, blood samples were examined for fasting triglycerides, high-density lipoprotein cholesterol and adiponectin levels. Results. The mean (±standard deviation) age, body mass index (BMI) and waist-to-hip ratio were 28.8±5.9 years, 27.1 ± 7.0 kg/m2 and 0.85±0.06, respectively. The prevalence of MS was 35.3%. Age, BMI, waist circumference and all metabolic parameters were higher in PCOS women with MS than in those without MS. MS prevalence increased with age, BMI and insulin resistance as determined by homeostasis model assessment (HOMA-IR), but not with adiponectin after BMI adjustment. Conclusions. According to the IDF criteria, one-third of the PCOS women had MS. This study also showed that age, BMI and HOMA-IR are important risk factors for MS.

Vitamin D receptor gene polymorphism is associated with urinary calcium excretion but not with bone mineral density in postmenopausal women

Polymorphism of vitamin D receptor (VDR) gene has been found to be associated with serum osteocalcin (OC) levels and bone mineral density (BMD) in Caucasian identical twins and unrelated postmenopausal women. Being ethnically different and living in a geographic area with adequate vitamin D status due to abundant sunshine exposure, it is unclear whether VDR gene polymorphism will affect bone mass in Thai population. In the present study, we investigated the association between VDR gene polymorphism and bone metabolism in Thai postmenopausal women. Subjects consisted of 84 postmenopausal women. Bsm I, Taq I and Apa I polymorphisms of VDR gene were determined by PCR-RFLP. B, T and A represent the absence of the corresponding restriction sites while b, t and a indicate the presence of the restriction sites. Data were expressed as mean ± SE. Sixty-six subjects (78.6%) had bb genotype while 18 (21.4%) had Bb genotype. None of the subjects was found to have BB genotype. Taq I restriction site was in linkage disequilibrium to the Bsm I site. For Apa I polymorphism, 33 (39.3%), 42 (50.0%) and 9 (10.7%) of the subjects had aa, Aa and AA genotypes, respectively. There was no significant difference in serum intact OC levels and BMD at various skeletal sites among subjects with different genotypes. Despite the lack of difference in BMD and intact OC levels, subjects with bb genotype had higher 24-hour urinary calcium excretion than those with Bb genotype (bb, 6.1 ±0.3 mmol/day; Bb, 4.4±0.6 mmol/day; p<0.05). The effect of Bsm I VDR genotype was still significant (p<0.05) after dietary calcium intake was controlled using analysis of covariance. Despite the difference in urinary calcium levels, there was no significant difference in fractional excretion of calcium among subjects with different Bsm I-related genotypes, suggesting that the effect of the VDR gene polymorphism on urinary calcium excretion is more likely due to the effect on intestinal calcium absorption rather than renal tubular calcium reabsorption. We conclude that VDR genotype distributions in Thai postmenopausal women are different from those reported in Caucasians. VDR gene polymorphism does not appear to be associated with BMD or bone turnover in Thai postmenopausal women. However, Bsm I VDR polymorphism may have physiologic role in calcium homeostatasis by modulating intestinal calcium absorption.

Reduced attenuation of bone resorption after oral glucose in type 2 diabetes

Objective  To investigate the effect of oral glucose on bone resorption and osteoprotegerin (OPG) in subjects with varying degrees of glucose tolerance.

Acanthosis nigricans: Clinical predictor of abnormal glucose tolerance in Asian women with polycystic ovary syndrome

The aim of this retrospective study was to assess whether acanthosis nigricans is a predictive factor for abnormal glucose tolerance (AGT) in Asian women with polycystic ovary syndrome (PCOS). Data from the record forms and electronic form of 121 PCOS women who consecutively attended the Reproductive Endocrinology and Infertility Unit were reviewed. In accordance with the units guidelines, all women received a physical examination, had anthropometric measurements taken and underwent as a 75-g oral glucose tolerance test after diagnosis. Their age, body mass index (BMI) and waist/hip ratio (WHR) was 29.1±6.1 years, 27.4±6.8 kg/m2 and 0.84±0.6 (mean±standard deviation), respectively. The prevalence of AGT was 42.9%, with 1.6% having impaired fasting glucose, 32.3% having impaired glucose tolerance and 9.1% having type 2 diabetes mellitus. The PCOS women with acanthosis nigricans had significantly higher BMI, WHR, fasting glucose, 2-h post-load glucose, fasting insulin, 2-h post-load insulin and prevalence of AGT compared with those without acanthosis nigricans. By logistic regression analysis, acanthosis nigricans and WHR were independent predictors for AGT, with an odds ratio (95% confidence interval) of 2.7 (1.1–7.1) and 10.1 (1.8–20.7), respectively. In conclusion, acanthosis nigricans was demonstrated as a predictive factor for AGT in Asian women with PCOS.

Association between Inflammatory Marker, Environmental Lead Exposure, and Glutathione S-Transferase Gene

A number of studies suggested that lead is related to the induction of oxidative stress, and alteration of immune response. In addition, modifying these toxic effects varied partly by GST polymorphism. The objectives of this study were to assess the association between the lead-induced alteration in serum hs-CRP, with GSTM1, GSTT1, and GSTP1 Val105Ile genetic variations and the health consequence from environmental lead exposure. The 924 blood samples were analyzed for blood lead, CRP, and genotyping of three genes with real-time PCR. Means of blood lead and serum hs-CRP were 5.45 μg/dL and 2.07 mg/L. Both CRP and systolic blood pressure levels were significantly higher for individuals with blood lead in quartile 4 (6.48–24.63 μg/dL) compared with those in quartile 1 (1.23–3.47 μg/dL, P < 0.01). In particular, in men with blood lead >6.47 μg/dL the adjusted odds ratio (OR) of CRP levels for individuals with GSTP1 variants allele, GSTM1 null, GSTT1 null, double-null GSTM1, and GSTT1 compared with wild-type allele was 1.46 (95% CI; 1.05–2.20), 1.32 (95% CI; 1.03–1.69), 1.65 (95% CI; 1.17–2.35), and 1.98 (95% CI; 1.47–2.55), respectively. Our findings suggested that lead exposure is associated with adverse changes in inflammatory marker and SBP. GST polymorphisms are among the genetic determinants related to lead-induced inflammatory response.

Association of a G2014A Transition in Exon 8 of the Estrogen Receptor-α Gene with Postmenopausal Osteoporosis

Abstract: We report the association of a newly identified synonymous G2014A single nucleotide polymorphism (SNP) which does not alter the amino acid sequence in exon 8 of the estrogen receptor-α (ERα) gene with osteoporosis in Thai postmenopausal women. Subjects consisted of 228 postmenopausal women aged more than 55 years divided into two groups – with vertebral or femoral osteoporosis (n= 106) or without osteoporosis (n= 122) – according to bone mineral density (BMD) criteria. The exon 8 G2014A SNP, which is 6 nucleotides upstream from the end of the stop codon, was identified by PCR-RFLP. Data are expressed as the mean and 95% CI. The allele frequency of the G2014A polymorphism was 26.4% in osteoporotic subjects and was significantly higher than that in non-osteoporotic women (15.2%) (p<0.05). By stepwise logistic regression analysis, it was found that the G2014A polymorphism was related to the presence of osteoporosis (odds ratio 2.7 per A allele, 95% CI 1.49–4.76) independently of body weight (odds ratio 0.93 per kg, 95% CI 0.89–0.96) and years since menopause (odds ratio 1.12 per year, 95% CI 1.08–1.19). In a multiple linear regression model, L2–L4 BMD of osteoporotic subjects was associated with body weight (p<0.05), endogenous estradiol levels (p<0.05) and the G2014A genotype (p<0.001), while it was related only to body weight (p<0.05) and estradiol levels in non-osteoporotic women (p<0.05). We conclude that a G2014A SNP in exon 8 of ERα is associated with the presence and severity of postmenopausal osteoporosis. Linkage disequilibrium between this polymorphism and the 3′-untranslated region of the ERα gene which may participate in the regulation of ERα gene expression remains to be determined.