Association of the ESR1 polymorphism with menopause and MLXIPL genetic variant influence serum uric acid levels in Slovak midlife women.

OBJECTIVE: This study examines associations between the ESR1 (XbaI, PvuII) and the MLXIPL (rs3812316) gene polymorphisms, and uric acid (UA) levels in Slovak midlife women, subdivided according to their menopause status. METHODS: We assessed a total of 362 women from 38 to 65 years of age. Women were recruited from different localities in the western and middle parts of Slovakia. Participants were interviewed during their medical examination at local health centers. They were investigated with respect to a variety of aspects such as medical, anthropometrical, and lifestyle. Participants provided a blood sample for biochemical analyses and DNA genotyping. The MLXIPL gene (rs3812316 SNP variant) and ESR1 gene (PvuII and XbaI) genotypes were then detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Data were analyzed using general linear models and multiple linear regression analyses to adjust for risk factors elevating the UA level such as fat mass (FM), triglycerides (TGs) and creatinine. RESULTS: A positive association between MLXIPL and UA level was observed in the total sample of women after control for confounding covariates, including FM, TGs, and creatinine (P = 0.027). Women with the CC genotype had higher UA levels than the G-allele carriers (261.5 µmol/L ± 68.3 vs 241.1 µmol/L ± 55.1 P = 0.013). A statistically significant association was noticed between postmenopause status and the ESR1 XbaI genotype and their effect on UA (P = 0.028). The Bonferroni pairwise comparison determined that the G-allele carriers in the postmenopausal period had higher estimated UA marginal mean (269.7 µmol/L) than the AA-allele postmenopausal women (236.5 µmol/L) (P = 0.012). The estimated UA marginal mean showed a significant increasing trend according to the MS in G allele carriers (248.5 µmol/L in pre/peri-menopausal vs 269.7 µmol/L in postmenopausal, P = 0.009). In contrast, a decreasing trend was observed in AA carriers (250.6 µmol/L in pre/perimenopausal women vs 236.5 µmol/L in postmenopausal). However, this trend was not statistically significant (P = 0.288). CONCLUSIONS: This cross-sectional study suggests that MLXIPL (rs3812316) polymorphism is associated with higher serum UA levels and that the ESR1 (XbaI) polymorphism is associated with UA levels only in the postmenopausal cohort.

Vasomotor, urogenital, psychological, and somatic symptoms in association with CYP1B1 polymorphisms in Slovak women of different menopausal status.

OBJECTIVES: The aim of this study was to examine if the Arg48Gly, Ala119Ser, Leu432Val, and Asn453Ser polymorphisms in the CYP1B1 estrogen-metabolizing gene are associated with menopausal symptom experience in healthy Slovak women aged 40-60 years. We also investigated the possible association of other factors with menopausal symptoms, including health status, physical activity, reproductive history, psychological status, and smoking. METHODS: The total sample consisted of 367 women (mean age 49.11 ± 5.86 years), encompassing 180 premenopausal (mean age 45.06 ± 3.81 years), 29 peri-menopausal (mean age 49.41 ± 3.94 years), and 158 postmenopausal (mean age 53.71 ± 4.54 years) women. The research comprised anthropometric and bioelectrical impedance analysis measurements (BIA), blood or saliva samples collected for DNA analysis, and a specific menopausal questionnaire. RESULTS: CYP1B1 Arg48Gly is significantly associated with vasomotor, psychological, and somatic symptoms. It appears that the Gly/Gly genotype is a risk factor during the postmenopause and protective in the pre- and peri-menopause. CYP1B1 Ala119Ser was associated with all menopausal symptoms, with the Ser/Ser genotype increasing risk in the premenopause and offering protection in the peri- and postmenopause. Polymorphisms Leu432Val and Asn453Ser gave unequivocal results; independent of menopausal status, the Leu/Leu genotype was associated with increasing risk of vasomotor, urogenital, and psychological symptoms and the Asn/Asn genotype provided a protective effect against psychological symptoms. CONCLUSIONS: Our results suggest possible associations of CYP1B1 polymorphisms with the occurrence and manifestation of particular menopausal symptoms in healthy mid-life Slovak women.

Genetic and Environmental Biomarkers Associated with Triglyceride Levels in Two Groups of Slovak Women.

OBJECTIVE: This study analyzed the association between the MLXIPL gene polymorphism (rs3812316) and triglyceride (TG) levels and selected environmental biomarkers in Slovak women at risk for cardiovascular disease compared to a reference sample. MATERIALS AND METHODS: The studied sample consisted of 200 women at cardiovascular risk (mean age 52.96 ± 6.01 years) and 244 healthy women (mean age 47.52 ± 5.34 years). Participants gave details of their health and lifestyle during their medical examination, and peripheral blood samples were used for biochemical analyses and DNA genotyping. A nested polymerase chain reaction-restriction fragment length polymorphism assay was used to detect the rs 3812316 SNP. RESULTS: We determined that there were significantly different genotype distributions in two TG categories: (1) subjects with normal TG values had a significantly higher G allele frequency than those with elevated TG levels (χ2 = 6.1556, df = 2, p = 0.046); and (2) the rare G allele frequency was 0.11 in the cardiovascular risk group and 0.15 in the reference group. Binary regression analysis showed that women with at least one G allele had a significantly lower relative risk of hypertriglyceridemia than women with the CC genotype (OR = 0.399, p = 0.022, 95% CI = 0.182-0.876). CONCLUSION: This cross-sectional study suggests that MLXIPL rs3812316 genotypes may be associated with TG levels. However, further analysis is advisable because of study limitations.

The association of Asn453Ser polymorphism in CYP1B1 gene with selected somatic and biochemical variables in Slovak women of different menopause status.

OBJECTIVE: The aim of this study was to determine the relationship between the CYP1B1 Asn453Ser polymorphism and selected somatic and biochemical variables, and atherogenic indices in premenopausal and postmenopausal Slovak women. METHODS: The studied sample consisted of 334 women; 188 premenopausal (mean age 45.73 ±â€Š3.77 y) and 146 postmenopausal women (mean age 53.51 ±â€Š4.52 y). The participants were interviewed during their medical examination. They provided a blood sample for biochemical analysis and DNA genotyping. RESULTS: The frequency of rare allele Ser (CYP1B14) was equal to 0.125 in premenopausal and 0.168 in postmenopausal women. The observed genotype frequencies were in the Hardy-Weinberg equilibrium. The Asn453Ser genotype showed statistically significant associations with a high-density lipoprotein (HDL-cholesterol) and apolipoprotein A1 levels in postmenopausal women. The mean values of the above mentioned variables were significantly higher in women carrying the Ser/Ser genotype. The general linear model analysis confirmed the results of the additive genetic model in postmenopausal women and demonstrated significant association of the Asn453Ser polymorphism with HDL-cholesterol levels also in premenopausal women (P = 0.041). CONCLUSIONS: This pilot study revealed a significant association of the CYP1B1 Asn453Ser genotypes with the plasma levels of HDL-cholesterol and of apolipoprotein A1 in postmenopausal women and less unequivocal findings in premenopausal women. Because of study limitations, these results need to be examined in a larger study.

Association of CILP2 and ACE gene polymorphisms with cardiovascular risk factors in Slovak midlife women.

The aim of this study is to assess the association of two polymorphisms, the cartilage intermediate layer protein 2 (CILP2) G/T and angiotensin converting enzyme (ACE) I/D, with blood pressure and anthropometrical and biochemical parameters related to the development of cardiovascular disease. The entire study sample comprised 341 women ranging in age from 39 to 65 years. The CILP2 genotypes were determined by PCR-RFLP and the ACE genotypes by PCR. The Bonferroni pairwise comparisons showed the effect of the CILP2 genotype on high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), apoB-to-apoA1 ratio, the total cholesterol (TC)-to-HDL-C ratio, non-HDL-C, and the LDL-C-to-HDL-C ratio (P < 0.05). Here, higher mean levels of HDL-C and lower mean levels of the remaining above mentioned lipid parameters were registered in the GT/TT genotype carriers than in GG carriers. Statistically significant association was identified between the ACE genotype and the following parameters: TC, LDL-C, and non-HDL-C (P < 0.05). The II genotype can lower serum level of TC (B = 0.40), LDL-C (B = 0.37), and non-HDL-C levels. The results of this study suggest that the minor T allele of CILP2 gene and I allele of ACE gene have a protective effect against elevated serum lipid and lipoprotein levels.

Power of biomarkers and their relative contributions to metabolic syndrome in Slovak adult women.

BACKGROUND: Metabolic syndrome (MetS) comprises a cluster of risk components which pre-dispose individuals to cardiovascular mortality. AIM: The purpose of this study is to investigate the variability of biochemical and anthropometric characteristics, apolipoprotein E (APOE) and angiotensin converting enzyme (ACE) genes and their contribution to MetS manifestation. SUBJECTS AND METHODS: A total of 438 adult women were recruited from different localities in Slovakia. All data was established by standard anthropometric, biochemical and genetic methods. RESULTS: The logarithm of the ratio of plasma concentration of triglycerides to HDL-cholesterol [log(TG-to-HDL-C)], waist circumference, systolic blood pressure, apolipoprotein A1, glucose and alanin aminotransferase accounted for most of the differences in MetS manifestation. Logistic regression showed that participants with risk values of the atherogenic index log(TG-to-HDL-C) had a 15.62-fold higher risk of MetS compared to those with lower values for this index (95% CI = 8.3-29.1). Women with hyperglycaemia (or formerly diagnosed diabetes mellitus) had an 8.82-times higher risk of MetS (95%CI = 3.22-24.16). Women with hyper-uricaemia had the same risk of MetS incidence as women with abdominal obesity, Exp (B) = 4.05.Hypercholesterolaemia, ACE and APOE genotypes did not influence MetS. CONCLUSION: MetS may involve many risk factors that can cause serious disorders in multiple organs. However, women with risk values involving plasma atherogenic index log (TG-to-HDL-C) experienced the highest risk of developing MetS.

Variant in the FTO gene and biomarkers related to health in mature Slovak women.

The purpose of this study was to investigate whether variant (rs178 17449, G/T) in the first intron of the fat mass and obesity-associated gene (FTO) was related to different obesity parameters and blood pressure in mature women from Slovakia. A total of 419 Slovak women (241 premenopausal and 178 postmenopausal) ranging in age from 39 to 65 years were recruited from different parts of Slovakia. The subgroups were categorized based on the WHO (1996) criteria. All participants gave written informed consent for participation in this study. Anthropometric parameters were measured using standard methods. Fat mass was examined by bioimpedance and blood pressure was measured in the morning during the medical examination. Genomic DNA was extracted from blood or saliva samples by the JET-QUICK Tissue DNA spine kit. The FTO variant was determined by PCR and restriction analysis according to the methodology of Hubacek et al. (2008). The obtained data were statistically analyzed by SPSS 17.0 for Windows. The FTO genotype and allele frequencies in the entire sample and in subgroups according to their menopausal and blood pressure status fell within the Hardy-Weinberg equilibrium. In postmenopausal women the FTO (rs178 17449) genotype was significantly associated with systolic blood pressure (SBP) (p = 0.024) in the dominant GG/GT vs.TT model and with diastolic blood pressure (DBP) (p = 0.030) in the recessive GG vs. GT/TT and the additive model (p = 0.043), respectively. In these postmenopausal women regression analysis showed a statistically significant effect of age, BMI and FTO dominant model on SBP, and of BMI on DBP among the other variables capable of inducing blood pressure differences. This study demonstrates that the SNP rs178 17449 in the FTO gene is associated with systolic and diastolic blood pressure but not with BMI and obesity variables, as already replicated in several populations throughout the world.

The association of cytochrome P450 1B1 Leu432Val polymorphism with biological markers of health and menopausal symptoms in Slovak midlife women.

OBJECTIVE: In this study, the CYP1B1 polymorphism was examined in relationship to recognized risk factors for cardiovascular disease. In particular, this study focused on plasma lipid levels, atherogenic indices, and body composition. Furthermore, this polymorphism was analyzed as a predisposing factor for menopausal symptoms among women during midlife, subdivided according to their menopause status. METHODS: A total of 399 women aged from 39 to 60 years were examined. They were recruited from the western and middle parts of Slovakia. Participants were interviewed during their medical examination, and they were investigated with respect to a variety of aspects such as anthropometric and medical aspects, and a menopause-specific questionnaire was included. The participants provided a saliva or blood sample for DNA genotyping and a blood sample for biochemical analysis. RESULTS: The Leu432Val genotype demonstrated statistically significant associations with triglycerides, with the ratio of total cholesterol to high-density lipoprotein cholesterol, and with the logarithm of the ratio of plasma concentration of triglycerides to high-density lipoprotein cholesterol in women in their reproductive period. The mean values were significantly lower in women carrying the Val/Val genotype. Four atherogenic indices showed a decreasing trend in relationship to the CYP1B1 genotypes in women during their reproductive period (in the following order of magnitude: Leu/Leu + Leu/Val vs Val/Val) and an increasing trend among postmenopausal women in the same order. Furthermore, the Val/Val genotype diminished experiences of bloated stomach, of vaginal dryness in perimenopausal and postmenopausal women, and of palpitations in premenopausal women. CONCLUSIONS: The Leu432Val polymorphism may be associated with the lipid profile in midlife women. Moreover, this polymorphism may influence the risk of some menopausal symptoms.

Menopausal complaints in Slovak midlife women and the impact of CYP1B1 polymorphism on their incidence.

A wide variety of symptoms have been attributed to menopause, negatively influencing women's physical and psychological health. In addition to lifestyle parameters and personal history, genetic factors are considered to be the main source of this variation. This study aims to investigate the incidence of menopausal symptoms among midlife women according to their menopausal status, and to evaluate the contribution to their manifestation from CYP1B1 Leu432Val polymorphism as a predisposing factor for menopausal symptoms. The studied cohort consisted of 299 women ranging from 39 to 59 years of age. Women were recruited from the western and middle parts of Slovakia, and all participants completed a menopause-specific questionnaire and provided blood or saliva samples for genotyping. Our results indicated that all women are at risk of typical menopausal symptoms, but there is a higher number of postmenopausal women affected than premenopausal ones. Regression analysis showed that the CYP1B1 Leu/Leu genotype can increase the experience of bloated stomach and facial hair increase in all the sampled women, while the Leu/Leu genotype may increase experience of palpitations and involuntary urination in the premenopausal women. The Leu/Leu genotype may increase the experience of nausea, bloated stomach, and vaginal dryness in peri- and postmenopausal women. We determined that women with the Leu/Leu, or Leu/Val genotypes were approximately five times more likely to suffer from vaginal dryness than the Val/Val women (OR = 4.948; 95% CI, 1.259-19.447). We therefore suggest that CYP1B1 Leu432Val polymorphism could be involved in individual susceptibility to menopausal symptoms in Slovak midlife women.

ACE insertion/deletion polymorphism and its relationships to the components of metabolic syndrome in elderly Slovaks.

The purpose of this study was to assess clustering of Metabolic Syndrome components in aged Slovaks, and to investigate whether insertion/deletion (I/D) polymorphism of the human angiotensin-converting enzyme (ACE) gene is associated with this syndrome. Data were available from 374 Slovak participants (200 females and 174 males) ranging in age between 60 and 90 years. ACE I/D polymorphism was determined by PCR amplification of the ACE gene sequence. Metabolic Syndrome was diagnosed according to criteria in the NCEP ATP-III. Elderly males and females differ significantly in the prevalence of Metabolic Syndrome (females 45.1%, males 24.8%). The males and females including subjects with and without metabolic syndrome, respectively, did not differ significantly in the three genotype distributions (p = 0.603 and p = 0.247). The allele frequencies (D = 0.5483, I = 0.4517) in the entire sample fell within the Hardy-Weinberg equilibrium. There was no confirmed association between ACE genotype and phenotypic variation in the recognized risk components for Metabolic Syndrome in elderly Slovaks. Among other factors which may induce a difference in Metabolic Syndrome, significant effect was detected for sex, BMI, HDL, TG, glucose and the ApoB/ApoA1 ratio.

Relationships between blood pressure, polymorphism of angiotensin-converting enzyme (ACE), body composition and biochemical characteristics in elderly Slovaks.

Epidemiological studies have demonstrated that several specific environmental factors and candidate genes influence the human variation in blood pressure. The aim of this study was to investigate variables associated with blood pressure; with a particular emphasis on the differences in insertion/deletion (I/D) polymorphism of the human angiotensin-converting enzyme (ACE), the body composition and the recognized risk factors for atherosclerosis among elderly males and females. A total of 374 participants (174 males and 200 females) aged from 60 to 90 years were recruited from different parts of Slovakia. The elderly were not bed-ridden, nor mentally impaired, they were able to manage their daily activities by themselves. The ACE I/D polymorphism was determined by PCR amplification of the ACE gene sequence. Body composition variables were obtained by bioelectrical impedance analysis, using the BIA 101 soft tissue-body impedance analyzer (Akern, S.r.l.). The subjects were determined to be hypertensive (blood pressure > or = 140/90 mm Hg) or normotensive (blood pressure < or = 140/90 mm Hg ). These two subgroups of males and females did not differ significantly in their mean ages. As expected, the hypertensive subjects of both sexes showed significantly higher mean values in systolic (SBP) and diastolic blood pressure (DBP), in body mass index (BMI), and in the mean values of their plasma glucose and extracellular water (ECW). The genotype distribution and allele frequencies in the whole sample (D = 0.5474, I = 0.4526) fell within the Hardy-Weinberg equilibrium. The frequency of the deleterious D allele in the normotensive (0.5532) and hypertensive (0.5516) subjects was not significantly different. The ACE I/D genotypes did not associate either with the systolic (p = 0.836) or diastolic BP (p = 0.629). From the other variables that may induce differences in blood pressure, a statistical effect was detected for glucose, Na/K, and Apo A1/ApoB ratios and physical activity on SBP, and for ApoA1, physical activity, BMI and total cholesterol on DBP.

International anthropometric study of facial morphology in various ethnic groups/races.

When anthropometric methods were introduced into clinical practice to quantify changes in the craniofacial framework, features distinguishing various races/ethnic groups were discovered. To treat congenital or post-traumatic facial disfigurements in members of these groups successfully, surgeons require access to craniofacial databases based on accurate anthropometric measurements. Normative data of facial measurements are indispensable to precise determination of the degree of deviations from the normal. The set of anthropometric measurements of the face in the population studied was gathered by an international team of scientists. Investigators in the country of the given ethnic group, experienced and/or specially trained in anthropometric methods, carried out the measurements. The normal range in each resultant database was then established, providing valuable information about major facial characteristics. Comparison of the ethnic groups' databases with the established norms of the North America whites (NAW) offered the most suitable way to select a method for successful treatment. The study group consisted of 1470 healthy subjects (18 to 30 years), 750 males and 720 females. The largest group (780 subjects, 53.1%) came from Europe, all of them Caucasians. Three were drawn from the Middle-East (180 subjects, 12.2%), five from Asia (300 subjects, 20.4%) and four from peoples of African origin (210 subjects, 14.3%). Their morphological characteristics were determined by 14 anthropometric measurements, 10 of them used already by classic facial artists, Leonardo da Vinci and Albrecht Dürer, complemented by four measurements from the nasal, labio-oral and ear regions. In the regions with single measurements, identical values to NAW in forehead height, mouth width, and ear height were found in 99.7% in both sexes, while in those with multiple measurements, vertical measurements revealed a higher frequency of identical values than horizontal ones. The orbital regions exhibited the greatest variations in identical and contrasting measurements in comparison to NAW. Nose heights and widths contrasted sharply: in relation to NAW the nose was very or extremely significantly wide in both sexes of Asian and Black ethnic groups. Among Caucasians, nose height significantly differed from NAW in three ethnic groups, with one shorter and two greater. In the Middle Eastern groups nose width was identical to those of NAW but the height was significantly greater. The present study, conducted by investigators working separately across the world and with small samples of the population, is clearly preliminary in nature and extent. Yet it may fulfill its mission if medical and anthropological investigators continue the work of establishing normative data of the face. These data are urgently needed by medical professionals but have been lacking up till now in western and northern Europe, Asia, and Africa.