Objective: The aromatization of androgenic precursors in peripheral tissues, including bone, is the main source of estrogens after the menopause. CYP19, the gene encoding aromatase, has a long 5 0 -untranslated region with several variants of exon I and specific promoters. The aim of this study was to investigate the possible relationship between a common biallelic (C/G) polymorphism located on exon I.2 and bone mineral density (BMD). Design: This was designed to be an association study between CYP19 polymorphism and BMD and the risk of vertebral fractures in women. Methods: DNA was extracted from the peripheral blood of 299 women (116 premenopausal and 183 postmenopausal). CYP19 alleles were identified by a method based on the exonuclease activity of Taq-polymerase. BMD was determined by dual-energy absorptiometry. Results: In premenopausal women there were no genotype-related differences in BMD. However, postmenopausal women with the CC genotype had lower spine and hip BMD than those with the GG genotype. The association between CYP19 genotypes and BMD was independent of other variables, such as age, height, body weight, calcium intake or years since menopause. The CC genotype was also associated with an increased risk of osteoporotic vertebral fractures (odds ratio 2.0; P ¼ 0.03). Serum levels of estrone and estradiol were similar in women with CC and GG alleles. Conclusions: A common biallelic polymorphism in the 5 0 -untranslated region of the CYP19-aromatase gene was associated with significant differences in bone mass and the risk of vertebral fractures in postmenopausal women. Given the frequency of allelic variants, genotype-related differences appear to be important from the perspective of the individual as well as the general population. Further studies are needed to elucidate underlying mechanisms that may be dependent on differences in estrogen bioactivity at the bone tissue level.European Journal of Endocrinology 150 699-704
OPG concentrations are associated with disease severity and CVD prevalence in patients with RA. Whether consideration of OPG concentrations can improve CVD risk stratification in RA merits future longitudinal investigation.
DACV is generally associated with antibiotics and NSAID. In most cases it has a favorable prognosis, although a small percentage of patients may develop residual renal damage.
Objective.In nondiabetic healthy individuals, insulin secretion and sensitivity are linked by a negative feedback loop characterized by a hyperbolic function. We aimed to study the association of traditional insulin resistance (IR) factors with insulin secretion and sensitivity, and to determine whether the hyperbolic equilibrium of this relation is preserved in patients with rheumatoid arthritis (RA).Methods.This was a cross-sectional study encompassing 361 nondiabetic individuals: 151 with RA and 210 controls. Insulin, C-peptide, and IR indices by homeostatic model (HOMA2) were assessed. A multivariable analysis was performed to evaluate the differences in the correlation of traditional IR-related factors with glucose homeostasis molecules, as well as IR indices between patients and controls. Nonlinear regression analysis was used to assess the hyperbolic relation of insulin sensitivity and secretion.Results.HOMA2-IR indices were higher in patients with RA than controls. Hepatic insulin extraction, as assessed by the insulin:C-peptide molar ratio, was lower in patients with RA after multivariable analysis (0.08 ± 0.02 vs 0.14 ± 0.07, p < 0.001). Traditional IR-related factors showed significantly lower adjusted correlation coefficients with IR indices in patients with RA. The association between insulin sensitivity and secretion showed a different hyperbolic relation in patients with RA: the variability explained by the curve was lower in RA (nonlinear r2 = 0.845 vs r2 = 0.928, p = 0.001) and β coefficients (−0.74, 95% CI −0.77 to −0.70 vs −1.09, 95% CI −1.17 to −1.02, ng/ml, p < 0.001) were different in RA.Conclusion.The traditional factors associated with IR in healthy individuals are less related to IR in patients with RA. Insulin sensitivity and secretion yield a different hyperbolic equilibrium in RA.
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