Background: Postmenopausal osteoporosis is a multifactorial disease. Genetic factors play an essential role in contributing to bone mineral density (BMD) variability, which ranges from 60 to 85%. Alendronate is used as the first line of pharmacological treatment for osteoporosis; however, some patients do not respond adequately to therapy with alendronate. Aim: The aim of this work was to investigate the influence of combinations of potential risk alleles (genetic profiles) associated with response to anti-osteoporotic treatment in postmenopausal women with primary osteoporosis. Methods: A total of 82 postmenopausal women with primary osteoporosis receiving alendronate (70 mg administered orally per week) for one year were observed. The bone mineral density (BMD; g/cm2) of the femoral neck and lumbar spine was measured. According to BMD change, patients were divided into two groups: responders and non-responders to alendronate therapy. Polymorphic variants in CYP19, ESR1, IL-6, PTHR1, TGFβ, OPG and RANKL genes were determined and profiles were generated from the combination of risk alleles. Results: A total of 56 subjects were responders to alendronate and 26 subjects were non-responders. Carriers of the G-C-G-C profile (constructed from rs700518, rs1800795, rs2073618 and rs3102735) were predisposed to response to alendronate treatment (p = 0.001). Conclusions: Our findings highlight the importance of the identified profiles for the pharmacogenetics of alendronate therapy in osteoporosis.
Alendronate are used as the first line of pharmacological treatment for osteoporosis; however, some of them do not respond adequately to therapy with alendronate. The aim of this study was to investigate the influence of combinations of potential risk alleles (genetic profiles) associated with the response to antiosteoporotic treatment in a cohort consisting of 82 postmenopausal women with primary osteoporosis receiving alendronate (70 mg administered orally per week) for one year. Bone mineral density (BMD; g/cm2) of the femoral neck and lumbar spine was measured. According to BMD change patients were divided in two groups: responders and non-responders to alendronate therapy. Polymorphic variants in CYP19, ER, IL-6, PTHR1, TGFβ, OPG and RANKL genes were determined and profiles generating from the combination of risk alleles. Results: 56 subjects were responders to alendronate and 26 subjects were non-responders. The carriers of A-C-T-C profile (constructed from rs700518, rs1800795, rs2073618, and rs3102735) were predisposed to response to alendronate treatment (P= 0.001). Our findings highlight the importance of identified profiles for pharmacogenetics of alendronate therapy in osteoporosis.
STAT4 plays an important role in disease activity in SLE patients. STAT4 particles have the capacity to activate the transcription of genes associated with the production of TH1 and Th17 lymphocytes, with a greater predominance on the production of IFN-γ and IL-17A. The presence of variants in STAT4 genes has a major impact on the generation of autoimmunity. However, there are few studies evaluating the impact of these variants on the production of proinflammatory cytokines such as IFN-γ and IL-17A. Methods—A case–control study was carried out with 206 Mexican mestizo patients residing in Western Mexico with a diagnosis of SLE and a group of 80 patients without autoimmune diseases was captured to determine the cut-off point for high IFN-γ levels. In this study, SLE patients with high IFN-γ levels were considered as cases (cut-off > 15.6 pg/mL), and SLE patients with normal IFN-γ levels were considered as controls (cut-off ≤ 15.6 pg/mL). Disease activity was identified from the systemic lupus erythematosus disease activity index (SLEDAI). For the determination of levels of cytokines IFN-γ, IL-12, and IL17A, commercial ELISA kits were used. Genotyping of STAT4 rs7574865 (G > T) was performed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. Results—The patients with SLE had a median age of 45 years with a range of disease duration from 4 years to 18 years; 45.6% were identified as having disease activity. In this sample, we identified a high IFN-γ prevalence of 35.4%. The levels of IFN-γ were higher in the patients with genotype TT than GG. We found that TT genotype conferred a higher risk of high IFN-γ when compared to the GG and GT genotypes. Conclusions—In this study, we identified that the polymorphic genotype TT of the STAT4 gene rs7574865 polymorphism is associated with increased levels of IFN-γ. However, its strength of association was weak, so complementary studies are needed to evaluate its impact on SLE patients.
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