FTO Gene Polymorphisms and Their Roles in Acromegaly.

The major causes of both morbidity and mortality in patients with acromegaly are cardiovascular diseases (CVDs). The polymorphisms of the fat mass and obesity-associated gene (FTO) are associated with obesity, as well as with an increased risk of CVDs. The aim of the study was to determine the relationship of risk alleles of four FTO gene polymorphisms with selected parameters of lipid and glucose metabolism as well as with IGF-1 and GH levels in the group of patients with acromegaly compared to the control group. The study group consisted of 104 patients with acromegaly and 64 healthy subjects constituting the control group. In the whole acromegaly group, the data reveal that the homozygous for risk allele carriers (rs1421085, rs9930506, rs9939609) as well as carriers of only one risk allele have lower IGF-1 concentrations. In the well-controlled acromegaly group, the homozygous for three risk allele carriers of FTO gene polymorphisms have lower HDL cholesterol concentration (rs1121980, rs1421085, rs993609). In the cured acromegaly group, homozygous risk allele carriers rs9930506 tend to have higher levels of total cholesterol and LDL cholesterol. These associations are not observed in the control group. Conclusion: there is an association between FTO gene polymorphisms and the metabolism of lipids, suggesting that the FTO gene may be associated with higher CVD risk in patients with acromegaly. In addition, there is an association between FTO gene polymorphisms and IGF-1, implying that FTO gene may influence/modify IGF-1 synthesis. Further investigation on a larger scale is required to provide more precise evidence.

Is H19 RNA a Useful Marker of Acromegaly and Its Complications? A Preliminary Study.

Acromegaly is a rare endocrine disorder caused by somatotroph pituitary adenoma. Besides its typical symptoms, it contributes to the development of cardiovascular, metabolic, and bone comorbidities. H19 RNA is a long non-coding RNA and it is suspected to be involved in tumorigenesis, cancer progression, and metastasis. H19 RNA is a novel biomarker for the diagnosis and monitoring of neoplasms. Moreover, there might be an association between H19 and cardiovascular and metabolic diseases. We enrolled 32 acromegaly patients and 25 controls. We investigated whether whole blood H19 RNA expression is associated with the diagnosis of acromegaly. Correlations between H19 and tumour dimension, invasiveness, and biochemical and hormonal parameters were evaluated. We analysed the coincidence of acromegaly comorbidities with H19 RNA expression. In the results, we did not observe a statistically significant difference in H19 RNA expression between acromegaly patients and the controls. There were no correlations between H19 and the adenoma size and infiltration and patients' biochemical and hormonal statuses. In the acromegaly group, hypertension, goitre, and cholelithiasis were observed more frequently. The diagnosis of acromegaly was a factor contributing to the occurrence of dyslipidaemia, goitre, and cholelithiasis. We found an association between H19 and cholelithiasis in acromegaly patients. To conclude, H19 RNA expression is not a relevant marker for diagnosis and monitoring of acromegaly patients. There is a higher risk of hypertension, goitre, and cholelithiasis related to acromegaly. Cholelithiasis is associated with a higher H19 RNA expression.

Ghrelin and Leptin Concentrations in Patients after SARS-CoV2 Infection.

SARS-CoV2 infection can lead to severe cytokine storm especially in obese patients. Ghrelin acts not only as an appetite regulator but can also play a key role in the immune reaction. Leptin, secreted mainly by the white adipose tissue, can act as a pro-inflammatory cytokine. The crucial question is whether or not the cytokine storm in COVID-19 patients with obesity is linked to adipokine dysregulation. The aim of this study was to assess ghrelin and leptin concentrations in patients 6 months after SARS-CoV2 infection in comparison to a control group considering the influence of sex. The study group included 53 patients with a history of COVID-19 and 87 healthy subjects in the control group. Leptin and ghrelin concentrations as well as hormonal and biochemical parameters were measured. A significantly higher ghrelin concentration was observed in the COVID-19 group in comparison to the control group, with a statistically significant impact of sex on the relationship between COVID-19 and ghrelin concentration, which was lower in the males. No statistically significant differences in leptin concentration were observed between the groups. A significant negative correlation was observed between ghrelin and testosterone and morning cortisol levels in the COVID-19 group. The current study showed that ghrelin levels were significantly higher in patients 6 months after a mild course of SARS-CoV2 infection. To confirm the hypothetical protective role of ghrelin in the inflammatory process, it would be necessary to compare serum ghrelin levels between patients after mild and severe courses of COVID-19. Due to the small sample size and the lack of patients with a severe course of COVID-19, these observations need further investigation. There were no differences in leptin concentrations between the COVID-19 patients and the control group.

Myokines in Acromegaly: An Altered Irisin Profile.

Introduction: The muscle is an endocrine organ controlling metabolic homeostasis. Irisin and myostatin are key myokines mediating this process. Acromegaly is a chronic disease with a wide spectrum of complications, including metabolic disturbances. Purpose: To examine the influence of acromegaly on irisin and myostatin secretion and their contribution to metabolic profile and body composition. Materials and Methods: In 43 patients with acromegaly and 60 controls, serum levels of irisin, myostatin, growth hormone (GH), insulin-like growth factor 1 (IGF-1), parameters of glucose, and lipid metabolism were determined. Body composition was assessed with dual-energy x-ray absorptiometry. Results: The irisin concentration was significantly lower in patients with acromegaly compared to controls (3.91 vs. 5.09 µg/ml, p = 0.006). There were no correlations between irisin and GH/IGF-1 levels. In the study group, irisin was negatively correlated with fasting insulin (r = -0.367; p = 0.042), HOMA-IR (r = -0.510; p = 0.011), and atherogenic factors: Castelli I (r = -0.416; p = 0.005), Castelli II (r = -0.400; p = 0.001), and atherogenic coefficient (AC) (r = -0.417; p = 0.05). Irisin and myostatin concentrations were also lower in acromegalics with insulin resistance than without (2.80 vs. 4.18 µg/ml, p = 0.047; 81.46 vs. 429.58 ng/L, p = 0.018, respectively). There were no differences between study group and controls in myostatin concentration. Myostatin levels negatively correlated with GH (r = -0.306; p = 0.049), HOMA-IR (r = -0.046; p = 0.411), and insulin levels (r = -0.429; p = 0.016). Conclusions: Decreased irisin concentrations in acromegaly may suggest impaired hormonal muscle function contributing to metabolic complications in this disorder. However, learning more about the association between myostatin and GH in acromegaly requires further studies. Nevertheless, it appears that myostatin is not critical for muscle mass regulation in acromegaly.

H19 in Endocrine System Tumours.

Long non-coding RNAs (lncRNAs) are over 200 nucleotides long recently discovered RNA molecules that are not involved in the translation process. Accumulating evidence shows that H19 lncRNA is an important regulator of gene expression and its altered expression contributes to carcinogenesis. The aim of this review was to reveal current knowledge about H19 lncRNA and its impact on tumours of the endocrine system. We present findings about H19 altered regulation and its association with tumorigenesis, cancer progression and differentiation, and its potential use in diagnostics, prognostics and therapy. The mechanism and molecular pathways involved in these processes are discussed.

Laboratory interference in the thyroid function test.

Thyroid hormones and thyroid-stimulating hormone (TSH) laboratory tests are commonly used worldwide, and their results have an important influence on decisions about treatment and further diagnostic processes. Any discrepancies between symptoms and laboratory results or between results of different tests should be closely investigated to avoid misdiagnosis and unnecessary treatment. Inconsistencies in hormone tests might be a result of physiological changes in hormonal balance, a disease, drug intake, or laboratory interference. Major factors that interfere with thyroid function tests are: heterophilic antibodies, macro TSH, biotin, thyroid hormones autoantibodies, anti-streptavidin, and anti-ruthenium antibodies. In this paper we discuss the influence of different factors on the procedures of hormonal immunoassays, as well as methods to minimise the risk of false results and misdiagnoses.

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 association between FTO gene polymorphism rs9939609 and obesity is sex-specific in the population of PURE study in Poland.

BACKGROUND: Fat mass and obesity-associated gene (FTO) polymorphism remains the strongest known genetic determinant of common obesity. However, its influence depends on ethnicity, and the FTO-mediated predisposition to other metabolic disturbances is questionable. OBJECTIVES: The aim of our study was to evaluate the association between FTO rs9939609 polymorphism and metabolic syndrome in a population of Prospective Urban Rural Epidemiology (PURE) study in Poland. MATERIAL AND METHODS: We enrolled 1,097 participants of the PURE study (683 women and 414 men) from the Lower Silesian voivodeship. Anthropometrical parameters and blood pressure were measured. Blood samples were taken for an examination of lipid profile and fasting glucose level. Genomic DNA was isolated and FTO polymorphism rs9939609 was genotyped. RESULTS: Male A-allele carriers had significantly higher mean body mass, body mass index (BMI), waist-to-hip ratio (WHR), and waist and hip circumferences than men without risk allele. They were also more often diagnosed with obesity on the basis of BMI and central obesity parameters. No such influence was observed in women. There were no significant associations between FTO polymorphism and metabolic syndrome or its components. CONCLUSIONS: Our results suggest a sex-specific association between FTO polymorphism and obesity traits. The occurrence of metabolic syndrome or its components was not related with FTO gene variation in our cohort.

Association of Vitamin D Receptor Polymorphisms With Activity of Acromegaly, Vitamin D Status and Risk of Osteoporotic Fractures in Acromegaly Patients.

Introduction: The vitamin D receptor (VDR) gene is one of the most widely studied tumorigenesis-related genes. The primary objective of this study was assessment of possible roles of VDR gene polymorphisms in acromegaly, with regard to the activity of the disease and compared them with a control group. Furthermore, we have assessed the associations between these polymorphisms with vitamin D status as well as with TBS (trabecular bone score) and risk for osteoporotic fracture in acromegaly patients. Materials and Methods: We studied 69 patients with acromegaly and 51 healthy controls (CG). Acromegaly patients were divided into three subgroups on the basis of disease activity (AA, active acromegaly; CD, controlled disease; CA, cured acromegaly). In all patients, blood samples were obtained to assess the hormonal and metabolic status as well as genetic analysis. VDR polymorphisms were determined by means of two methods, Polymerase Chain Reactions (PCR) and minisequencing (SNaPshot). Results: Genotype frequencies for VDR ApaI, TaqI, BsmI, and FokI polymorphisms did not deviate significantly from Hardy-Weinberg equilibrium (HWE) in the acromegaly group as well as in the control group. There was no statistically significant difference in distributions of these four VDR genotypes between acromegaly patients and the control group. This study revealed statistically significant negative correlation between risk of major osteoporotic fractures and genotypes tt (TaqI), aa (ApaI) and bb (BsmI) in acromegaly groups. Furthermore, the negative correlations were observed between TBS and risk for major osteoporotic fractures and hip fractures. Conclusions: Our study suggests that tt (TaqI), aa (ApaI) and bb (BsmI) of VDR gene may be associated with better bone quality and microarchitecture (higher TBS), which lead to a lower risk of osteoporotic fractures in acromegaly patients. TBS may be a useful tool for predicting risk of fractures in acromegaly patients.

Turner syndrome and Cushing disease - the coexistence with overlapping complications: case report and literature review.

We present an unusual case of Turner syndrome (TS) and Cushing disease (CD) in a young woman, admitted to our department seven years after a successful surgical removal of ACTH-secreting pituitary tumor. To our knowledge, this is the first ever report of these two disorders coexisting. Our patient was diagnosed with TS at the age of 16 due to primary amenorrhea and short stature. Hormone replacement therapy with estrogen was initiated, but she did not receive growth hormone therapy. At the age of 28, she developed clinical and biochemical abnormalities consistent with hypercortisolism, but the definitive diagnosis of CD was established nine years later when she was admitted to our department. Appropriate treatment was applied, however, the patient developed serious complications: a myocardial infarction, diabetes and osteoporosis. Surgical treatment appeared to improve some, but not all of the symptoms, indicating a significant contribution of concomitant TS to the severity of adverse cardiovascular and bone turnover outcomes in a subject with a genetic susceptibility to these complications. Thus, multidisciplinary evaluation in such patients is strongly indicated, particularly if more predisposing conditions are present.

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.

Determinants of obesity in population of PURE study from Lower Silesia.

INTRODUCTION: The knowledge about obesity pathogenesis is insufficient. The aim of our study was to investigate environmental and individual determinants of obesity in population of PURE study from Lower Silesia. MATERIAL AND METHODS: This was a cross sectional observation of 1064 inhabitants of Wroclaw and neighbouring rural area (671 women, 393 men), who took part in PURE study in years 2007-2010. Each participant answered PURE questionnaire and International Physical Activity Questionnaire providing information about obesity risk factors. Anthropometric measurements were collected, blood samples were taken for assessment of FTO gene polymorphism. A stepwise logistic regression analysis was performed to identify the most significant predictors of obesity. RESULTS: 31% of the study group had obesity (BMI over 30 kg/m², no difference between men and women), overweight (BMI 25-29.9 kg/m²) affected 48.1% of men and 36.7% of women. Determinants of obesity in female group were: rural inhabitancy, chronic medication, unemployment, age, sedentary leisure time activity, non-smoking, hypertension in family, family related stress (p = 0.66 in the Hosmer-Lemeshow test). Determinants of obesity in male group were rural inhabitancy, chronic medication, family related stress, diabetes in family (p = 0.27 in the Hosmer-Lemeshow test). Risk factors for central obesity were similar, however in women oral contraception and physical activity were associated with lower obesity risk. CONCLUSIONS: Environmental factors, especially rural inhabitancy and family related stress were associated with higher obesity risk in our study. Employment, smoking, physical activity and use of oral contraception seemed to have protective role in women.

Preptin in women with polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) patients, frequently develop metabolic complications, such as insulin resistance (IR), impaired carbohydrate metabolism, dyslipidemia, obesity. Among the new markers responsible for metabolic disorders, preptin seems to be of great significance. MATERIAL: One hundred and thirty-four women aged 17-45 were enrolled. PCOS was diagnosed in 73 women on the basis of ESHRE-ASRM criteria. Non-PCOS group consisted of 61 women with regular menstruation matched for nutritional status. METHODS: All women underwent anamnesis, physical examination, anthropometric measurements, the abdominal ultrasound examination, and dual energy X-ray absorptiometry (DXA). Serum adropin levels were determined by ELISA. Biochemical and hormonal (testosterone, androstenedione, LH, FSH, estradiol) measurements were also performed. Insulin resistance indices (HOMA, QUICKI, Matsuda) and free androgen index (FAI) were calculated with the test results according to the standard formula. For all comparisons, statistical significance was defined by p ≤ .05. RESULTS: Serum preptin levels were significantly higher in the PCOS group. No significant correlations between preptin level and metabolic and hormonal markers were observed. The logistic regression analysis demonstrated that serum preptin level was an independent factor differentiating the two groups. CONCLUSIONS: Serum preptin levels were significantly higher in women with PCOS compared with controls. This peptide might be an independent predictor of PCOS in the future.

Association between FTO gene polymorphisms and HDL cholesterol concentration may cause higher risk of cardiovascular disease in patients with acromegaly.

INTRODUCTION: Cardiovascular diseases are main cause of morbidity and mortality in acromegaly. Polymorphisms of FTO gene are associated with obesity and increased risk of CVD (independently of BMI). Aim of this study was to investigate the allele frequencies of two FTO gene polymorphisms: rs9939609 and rs9930506 in patients with acromegaly and to examine the association of FTO gene polymorphisms with BMI and selected metabolic parameters. MATERIALS AND METHODS: Identification of two single nucleotide polymorphisms of FTO gene was carried out in 51 patients with acromegaly using the minisequencing method. RESULTS: The risk-allele frequencies of rs9939609 and rs9930506 polymorphisms were 0.471 and 0.529, respectively and they were higher than in general European population. There is no association of FTO gene polymorphisms with BMI, glucose, total cholesterol, LDL cholesterol and triglyceride. The risk alleles were associated with decreased HDL cholesterol concentration. Homozygotes for the rs9939609-risk allele had 1.25-fold lower HDL cholesterol concentration than carriers of the TT genotype (p = 0.0024). The estimated average decrease in HDL cholesterol concentration per risk allele for rs9930506 was 11.2%. Nevertheless, statistically significant differences were observed only between AG versus GG and AA versus GG genotypes. Homozygotes for the rs9930506-risk allele had 1.27-fold lower HDL cholesterol concentration than carriers of the AA genotype (p = 0.007). CONCLUSION: The risk-allele frequencies of studied polymorphisms in acromegaly were higher than in general European population. There is an association between FTO gene polymorphisms and HDL cholesterol concentration, suggesting FTO gene polymorphisms may be associated with higher CVD risk in patients with acromegaly.

The Frequencies of Haplotypes of FTO Gene Variants and Their Association with the Distribution of Body Fat in Non-Obese Poles.

BACKGROUND: The minor allele frequencies (MAFs) of the FTO gene vary substantially among different ethnic groups, and this variation may explain, to some degree, the differences between estimates of the effects of these alleles on body fat distribution indicators. OBJECTIVES: The aim of this study was to investigate the prevalence of fat mass and obesity associated (FTO) gene variants characterizing the structure of FTO haplotypes in a large Polish population, and to examine the influence of FTO gene variants on body fat distribution among metabolically obese normal weight (MONW) individuals, i.e. those with a normal BMI and visceral obesity. MATERIAL AND METHODS: A total of 854 non-obese individuals aged from 20 to 40 years, residing in three different regions in Poland, were studied. All the patients from this group were genotyped for four FTO gene variants (rs9939609, rs9930506, rs1421085 and rs1121980). Simultaneous identification of all single nucleotide polymorphisms (SNPs) was conducted using the minisequencing method with a pair of designed specific primers. RESULTS: Over 90% of the diplotypes contain only the two most common haplotypes, in three combinations of haplotype pairs: CTAT/CTAT comprised 26.9% in women and 30.9% in men; CTAT/TCGA comprised 45.0% in women and 44.4% in men; and TCGA/TCGA comprised 19.3% in woman and 14.8% in men. The analysis of the variance in body fat distribution parameters shows no statistically significant differences between the three common haplotype pairs in either men or women. CONCLUSIONS: The young Polish population is characterized by two disparate haplotypes of common FTO gene variants: TCGA (a risk SNP haplotype), and CTAT (a protective haplotype). No significant differences were found between fat distribution indicators in relation to haplotypes in either women and men.

Association of serum glypican-4 levels with cardiovascular risk predictors in women with polycystic ovary syndrome - a pilot study.

OBJECTIVE: Glypican-4 (Gpc4) is an adipokine which interacts with the insulin receptor and affects insulin sensitivity in proteoglycans. Insulin resistance plays a crucial role in the etiology of polycystic ovary syndrome (PCOS). PCOS is associated with metabolic disturbances such as abdominal obesity, dyslipidemia and type 2 diabetes. Thus, higher levels of Gpc4 released from visceral adipose tissue in women with PCOS may suggest an increased risk of cardiovascular disease (CVD). DESIGN: The aim of this pilot study was to determine whether the serum Gpc4 level is associated with cardiovascular risk predictors in women with PCOS. METHODS: Sixty-two women with PCOS according to the Rotterdam criteria (20-35 years old) and 43 healthy controls were studied. Cardiovascular risk predictors such as obesity indices, fat deposits according to dual-energy X-ray absorptiometry, biochemical lipid profile parameters and Homeostasis Model Assessment were estimated. RESULTS: The serum Gpc4 level in PCOS women was significantly higher (2.61 ± 1.17 ng/ml) than in the control group (1.55 ± 0.47 ng/ml) and correlated with waist circumference, waist-to-hip ratio, total fat and android fat deposit to gynoid fat deposit ratio only in the PCOS group. CONCLUSION: The Gpc4 level was higher in the PCOS group and correlated with CVD risk predictors, especially fat distribution.

Irisin plasma concentration in PCOS and healthy subjects is related to body fat content and android fat distribution.

Irisin (Ir), a recently identified adipo-myokine, cleaved and secreted from the protein FNDC5 in response to physical activity, has been postulated to induce the differentiation of a subset of white adipocytes into brown fat and to mediate the beneficial effects on metabolic homeostasis. Metabolic syndrome (MS), a cluster of factors leading to impaired energy homeostasis, affects a significant proportion of subjects suffering from polycystic ovary syndrome (PCOS). The aim of our study was to investigate the relationship between Ir plasma concentrations and metabolic disturbances. The study group consisted of 179 PCOS patients and a population of 122 healthy controls (both groups aged 25-35 years). A subset of 90 subjects with MS was isolated. A positive association between Ir plasma level and MS in the whole group and in controls was found. In subjects with high adipose body content (>40%), Ir was higher than in lean persons (<30%). Our results showed a significant positive association between Ir concentration and android type of adipose tissue in the whole study group and in the control group. Understanding the role of Ir in increased energy expenditure may lead to the development of new therapeutics for obesity and obesity-related diseases.

[Irisin--a new mediator of energy homeostasis]. / Iryzyna ­ nowy mediator homeostazy energetycznej

Skeletal muscles as an active hormonal compartment in the response of physical activity secrete substances named myokines capable of modulating metabolic processes. Myokines take part in communication between muscles and other tissues. Irisin (Ir) - a newly discovered adipomyokine - is cleaved and secreted to the circulation from a fibronectin type III domain containing protein 5 (FNDC5). The mechanism of Ir action has not been described precisely, and receptors for the molecule are not defined yet, but it has been proposed to promote browning of white adipose tissue into beige fat cells. To date we have distinguished two types of adipose tissue in mammals - white, which not only functions as a store of energy but also can play a pro-inflammatory role (secreting adipokines), and brown adipose tissue. Brown adipose tissue has a high mitochondrial content and can dissipate chemical energy in the form of heat (nonshivering termogenesis). It plays a natural antiobesity role and protects against obesity-related diseases. The development of beige adipose tissue, which in its structure and function is similar to brown adipose tissue, and the possibility to modify its amount through some external factors, are nowadays among the most important targets of research on fat cell biology.

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.

Interrelation between genotypes of the vitamin D receptor gene and serum sex hormone concentrations in the Polish elderly population: the PolSenior study.

AIM: Vitamin D co-regulates the synthesis of sex hormones. Therefore, the aim of this study was to determine whether the presence of certain genotypes of the vitamin D receptor gene (VDR) is associated with the serum levels of sex hormones in the elderly Polish population. MATERIALS AND METHODS: The rs10735810, rs1544410, rs7975232, and rs731236 polymorphisms of VDR, the serum levels of testosterone and estradiol, as well as free estrogen index (FEI) and free androgen index (FAI) were evaluated in 360 women and 400 men aged 65-90years selected from 5695 respondents of the PolSenior survey. RESULTS: Only the rs1544410 VDR polymorphism was associated with the serum levels of sex hormones. The prevalence of rs1544410 genotypes was 38% BB, 46% Bb, and 16% bb in women and 41% BB, 44% Bb, and 15% bb in men. In women the frequency of the B allele was p=0.61 and b allele q=0.39, while in men it was p=0.63 and q=0.37, respectively. We found significant differences in the serum testosterone level (p<0.0004) and FAI (p<0.0015) between the rs1544410 genotypes in women but not in men. Higher mean testosterone level and higher mean FAI were observed in women with a rare bb genotype in comparison to a common BB genotype. CONCLUSION: We hypothesize that in women the increase in VDR expression associated with a rare genotype of the rs1544410 polymorphism of this gene may be associated with an increase in testosterone and FAI levels.