Trabecular bone score and sclerostin concentrations in patients with primary adrenal insufficiency.

Background: Patients with primary adrenal insufficiency need lifelong replacement therapy with glucocorticoids and mineralocorticoids, which may influence their bone quality. Aim: The aim of the study was to evaluate densitometry parameters, trabecular bone score and sclerostin concentrations in patients with primary adrenal insufficiency in comparison to control group. Materials and methods: We included 29 patients (62% females) with diagnose of autoimmune primary adrenal insufficiency (mean age 49.7 ± 11.7 years, mean duration of the disease 13.2± 13.6 years) and 33 healthy subjects (adjusted with age, sex and body mass index). Bone mineral density at the femoral neck, lumbar spine, total body and trabecular bone score were evaluated. Serum sclerostin concentrations were measured. Results: There were no significant differences in densitometry parameters (T-score, Z-score, bone mineral density in all locations) as well as in trabecular bone score in patients with adrenal insufficiency in comparison to control group. Mean serum sclerostin concentration was significantly higher in patients with adrenal insufficiency than in control group (44.7 ± 23.5 vs 30.7 ± 10.4 pmol/l, p=0.006). There was a negative correlation between trabecular bone score and the duration of adrenal insufficiency and age, also a negative correlation between femoral neck and total densitometry parameters and 24-hour urine cortisol as a marker of hydrocortisone daily dose in patients with adrenal insufficiency. Conclusions: The bone status in patients with primary adrenal insufficiency was not impaired in comparison to control group, while sclerostin concentration was higher. The duration of the disease and higher hydrocortisone doses may affect negatively bone status.

The FTO gene is not associated with weight gain during six years of observation in the population of the PURE study in Poland.

INTRODUCTION: We present the first longitudinal study in Poland analysing the association between fat mass and obesity-associated gene (FTO) polymorphism and changes in anthropometric parameters. MATERIAL AND METHODS: 1120 participants of the Prospective Urban Rural (PURE) study in Poland (mean age 53.7 years) were genotyped for FTO gene polymorphism (rs9939609, rs9930506, rs1421085, rs1121980). Anthropometric parameters were measured at three time points (baseline, after three years, and after six years of observation). RESULTS: The mean body mass index (BMI) in the study group was 28 kg/m². Overall, there was a significant increase in the mean weight, BMI, and waist size during the six years (p≈0). Although males initially weighed more than females (p = 0), over the whole six-year period women had a greater tendency to increase in weight (p = 0.068), BMI (p = 0.014), and waist size (p = 0.041). Subjects with at least one A allele at rs9939609 initially weighed more on average (77.5vs. 74.7 kg, p = 0.027) and had a greater waist size (92 vs. 89.5 cm, p = 0.025) than those with the TT genotype. The differences in baseline results were more expressed in males than in females. There is no association between the changes in anthropometric parameters over the whole study period of six years and the FTO gene. CONCLUSIONS: FTO gene polymorphism is associated with anthropometric parameters in participants from the PURE study in Poland. However, there is no association between the presence of risk alleles and changes of anthropometric parameters over six years of observation.

The Influence of FTO Polymorphism rs9939609 on Obesity, Some Clinical Features, and Disturbance of Carbohydrate Metabolism in Patients with Psoriasis.

BACKGROUND: Psoriasis is often accompanied by obesity, hyperlipidemia, diabetes, and metabolic syndrome as risk factors of cardiovascular conditions and premature mortality. OBJECTIVE: The study was aimed at investigating whether psoriatic patients, who carry risk allele of obesity-related FTO gene, are more predisposed to obesity and metabolic disturbances and whether it influences the severity of psoriasis. METHODS: 197 patients with psoriasis, representing Lower Silesia region of Poland, underwent physical examination and anthropometric measurements. Blood samples for biochemical and genetic analysis were collected. All patients were genotyped for FTO gene rs9939609 variant. Identification of SNP was conducted with the use of minisequencing method. RESULTS: Around 63% of patients were carriers of at least one risk allele A and 20% were AA homozygotes. The A allele was associated with increased BMI and hip and waist circumferences. The carriers of risk allele had increased PASI and CRP values and tended to have an increased insulin concentration. CONCLUSION: Psoriatic patients, carriers of risk allele of FTO gene rs9939609, have an increased risk for more severe psoriasis and obesity and may develop obesity-induced insulin resistance.

Genetic Variation in One-Carbon Metabolism and Changes in Metabolic Parameters in First-Episode Schizophrenia Patients.

Background: In this study, we aimed to investigate the effects of polymorphisms in genes encoding 1-carbon metabolism enzymes on differential development of metabolic parameters during 12 weeks of treatment with second-generation antipsychotics in first-episode schizophrenia patients. Methods: The following polymorphisms in 1-carbon metabolism genes were genotyped: MTHFR (C677T and A1298C), MTHFD1 (G1958A), MTRR (A66G), and BHMT (G742A). A broad panel of metabolic parameters including body mass index, waist circumference, total cholesterol low and high density lipoproteins, triglycerides, homocysteine, folate, and vitamin B12 was determined. Results: There was a significant effect of the interaction between the MTHFR C677T polymorphism and time on body mass index and waist circumference in the allelic and genotype analyses. Indeed, patients with the MTHFR 677CC genotype had higher increase in body mass index and waist circumference compared with other corresponding genotypes or the MTHFR 677T allele carriers (CT and TT genotypes). In addition, patients with the MTHFR 677TT genotype had higher waist circumference in all time points. Similarly, patients with the MTHFR 677TT genotype had higher body mass index in all time points, but this effect was not significant after correction for multiple testing. Conclusions: Our results indicate that the MTHFR C677T polymorphism may predict antipsychotic-induced weight gain. Effects of the MTHFR C677T polymorphism might be different in initial exposure to antipsychotics compared with long-term perspective.

Metabolic dysregulation in first-episode schizophrenia patients with respect to genetic variation in one-carbon metabolism.

The aim of this study was to investigate the prevalence of metabolic disturbances in patients with first-episode schizophrenia (FES) and test the hypothesis that genetic variation in one-carbon metabolism may account for metabolic dysregulation in early psychosis. We measured fasting glucose, lipid profile parameters, homocysteine, folate and vitamin B12 in 135 patients with FES and 146 healthy controls (HCs). Polymorphisms in the following genes were determined: MTHFR (C677T and A1298C), MTHFD1 (G1958A), MTRR (A66G) and BHMT (G742A). Serum levels of folate and high-density lipoproteins (HDL) were significantly lower in patients with FES compared to HCs. In turn, serum levels of homocysteine and triglycerides were significantly higher in patients with FES than in HCs. Prevalence of hyperhomocysteinemia, low folate and HDL levels together with dyslipidemia was significantly higher in patients with FES compared to HCs. Higher homocysteine levels, lower vitamin B12 levels and the presence of metabolic syndrome were associated with higher severity of negative symptoms. None of studied polymorphisms was associated with schizophrenia risk. Several associations between studied polymorphisms and cardio-metabolic parameters were found. None of them remained significant after Bonferroni correction. Our results indicate that metabolic dysregulation in patients with FES is not associated with genetic variation in one-carbon metabolism.

Vitamin D receptor gene polymorphisms in Alzheimer's disease patients.

THE AIM: The aim of this study was to determine whether polymorphisms of the VDR gene may increase the risk of Alzheimer disease (AD) development in Lower Silesian patients in comparison with other populations. MATERIAL AND METHODS: 108 AD patients (aged 73.7±8.6) vs 77 healthy volunteers (aged 64.5±7.8) in the Lower Silesian population were studied. We investigated the frequency of the VDR polymorphisms rs731236 (TaqI), rs7975232 (ApaI), rs10735810 (FokI) and rs1544410 (BsmI) in the AD group vs the healthy group. Afterwards, MEDLINE and ResearchGate were studied to compare our investigation with other populations, due to the relatively small group size in our study. RESULTS: We did not observe any significant differences in frequency of genotypes of rs731236 (TaqI), rs10735810 (FokI) or rs1544410 (BsmI) VDR polymorphisms between the two Lower Silesian groups. Frequency of allele A of ApaI in the control group was significantly higher vs AD patients (p<0.0177) in the Lower Silesian population. Furthermore the difference in the occurrence of allele t in TaqI and allele A in ApaI between AD patients vs the control group was significant (respectively p<0.0056, p<0.0140) in British Europeans. This observation may suggest that allele "a" of the ApaI polymorphism is a risk allele in AD Lower Silesian patients. We compared our results with those obtained for the population of British Europeans. In multivariate stepwise regression, allele "A" of ApaI was associated with 30% lower risk of AD (OR=0.70, p=0.0009) in total treated Polish and British populations. We did not observe similar results in Turkish and Iranian populations. CONCLUSION: Our data suggest that the allele "A" VDR genotype of ApaI reduces AD risk, probably depending on ethnic origin and climatic conditions.

Association between vitamin D concentration and levels of sex hormones in an elderly Polish population with different genotypes of VDR polymorphisms (rs10735810, rs1544410, rs7975232, rs731236).

BACKGROUND: Vitamin D co-regulates the synthesis of sex hormones in part by interaction with its nuclear receptor. The aim of this study was to determine whether there is an association of vitamin D concentration vs the level of sex hormones in elderly Polish individuals with different genotypes of the vitamin D receptor (VDR) gene. MATERIALS AND METHODS: Rs10735810, rs1544410, rs7975232, and rs731236 polymorphisms of VDR, the serum sex hormone level, free estrogen index (FEI) and free androgen index (FAI) as well as vitamin D, were evaluated in 766 persons (362 women and 404 men) selected from 5695 Polish population, aged 65-90years from the PolSenior survey. RESULTS: We observed that women with GG (rs731236), TT (rs7975232), BB (rs1544410) and FF (rs10735810) genotypes were characterized by a significant correlation between vitamin D vs testosterone concentration and FAI value. We found a significant correlation between testosterone level and FAI vs vitamin D concentration in men with heterozygote AG in the rs731236 polymorphism and in the GG (rs7975232), the BB (rs1544410), and the Ff (rs10735810) genotypes. CONCLUSION: In elderly selected Polish population with different genotypes of VDR polymorphisms, a statistically significant relationship between vitamin D concentration vs testosterone level was observed.

Selected CNR1 polymorphisms and hyperandrogenemia as well as fat mass and fat distribution in women with polycystic ovary syndrome.

The endocannabinoid system is postulated to play an important role in the etiology of obesity, insulin resistance, fat distribution and metabolic disorders. Insulin resistance associated with abdominal obesity plays a leading role in the etiology of hyperandrogenism and other clinical features of the polycystic ovary syndrome (PCOS). A total of 174 women 16-38 years old, diagnosed with PCOS according to the Rotterdam criteria are recruited. Control group consisted of 125 healthy women 18-45 years old. Medical history, physical examination, anthropometric parameters and metabolic parameters were carried out. Six CNR1 gene polymorphisms were diagnosed. We observed a significantly three times higher risk of GG genotype in the polymorphism rs12720071 in women with PCOS versus the control group (p = 0.0344, OR = 3.01). A similar, significant 8-fold higher risk (p = 0.0176, OR = 8.81) was demonstrated for genotype CC polymorphism rs806368 associated with PCOS. We observed a 3.6-fold increased risk of hyperandrogenemia (free androgen index - FAI > 7) in patients with GG genotype in the rs12720071 polymorphism and AA genotype in the polymorphism rs1049353 (OR = 2.7). Our study may indicate a role of the endocannabinoid system in the occurrence of a specific hyperandrogenemia phenotype of PCOS.