Polymorphism In Postmenopausal Women Research Articles

Investigating the Interplay of Lipid Profile and Sex Hormone binding globulin Gene Polymorphism in Postmenopausal Women with Type 2 Diabetes

Investigating the Interplay of Lipid Profile and Sex Hormone binding globulin Gene Polymorphism in Postmenopausal Women with Type 2 Diabetes

Polymorphisms of genes of interleukin-6 and alpha-1 chain of collagen type 1 in postmenopausal women with knee osteoarthritis

BACKGROUND: To date in the Russian Federation insufficient attention has been paid to the study of IL6 and COL1A1 gene polymorphisms role in the development of knee osteoarthritis. And the results of the single carried out to date studies, devoted to the research of polymorphic variants of the above genes influence on the osteoarthritis development, are insufficient for substantiated conclusions.
 AIM: To study the frequency of alleles and genotypes of the IL6 gene rs1800795 polymorphism and COL1A1 gene rs1107946 and rs1800012 polymorphisms in postmenopausal women with knee osteoarthritis.
 MATERIALS AND METHODS: The results of 157 postmenopausal women survey with knee osteoarthritis were selected and analyzed. The control group consisted of 326 women of the same age without signs of joint disease. The study of polymorphisms rs1800795, rs1107946 and rs1800012 was performed by real-time polymerase chain reaction.
 RESULTS: The conducted studies showed that in the general group of examined women the frequency of all three studied polymorphisms genotypes registration corresponded to the Hardy-Weinberg law. An uneven (p = 0.043) distribution of rs1800795 polymorphism genotypes was found in the group of women with osteoarthritis and in the control group in the study of the IL6 gene polymorphic variants frequency detection. This difference was due to more frequent GG genotype registration of the above polymorphism (odds ratio = 1.75; 95% confidence interval: 1.12–2.72; p = 0.021) among women with knee osteoarthritis. Associations of rs1107946 and rs1800012 COL1A1 gene polymorphisms were not found (p 0.05).
 CONCLUSIONS: An association between GG genotype of the IL6 gene rs1800795 polymorphism and knee osteoarthritis in postmenopausal women has been established. Genotypes and alleles of COL1A1 gene rs1107946 and rs1800012 polymorphisms were not associated with joint disease.

Association Between Vitamin D Levels and Vitamin D Receptor FokI Polymorphism in Thai Postmenopausal Women With Osteoporosis

Background: Osteoporosis is a complex genetic disease, which is common among postmenopausal women. It is characterized by decreased bone mineral density (BMD) and increased bone fragility and fractures.
 Objective: To study the association between serum vitamin D levels and vitamin D receptor (VDR) genetic FokI polymorphism in postmenopausal women with osteoporosis.
 Methods: A total of 60 postmenopausal women who came for treatment at the menopausal clinic at Ramathibodi Hospital were enrolled. All of the patients had their BMD measured, and were determined serum vitamin D levels and VDR FokI polymorphism. Data were analyzed using chi-square and Fisher exact tests. The frequency of single nucleotide polymorphism (SNP) with risk of osteoporosis was compared.
 Results: Among 60 postmenopausal women, 26 (43.3%) women were an osteoporotic group and 34 (56.7%) women were non-osteoporotic group. There were no significant differences in age, vitamin D levels, or VDR FokI polymorphism between the groups (P > .05). However, the TT genotype of VDR FokI polymorphism was significantly associated with vitamin D deficiency (< 20 ng/mL) (OR, 6.15; 95% CI, 1.51 - 25.14; P < .05).
 Conclusions: Vitamin D levels and genotype of VDR FokI polymorphisms were similar between the osteoporotic and non-osteoporotic postmenopausal women. The TT genotype of VDR FokI polymorphism showed a significant association with vitamin D deficiency. Therefore, TT genotype of VDR FokI polymorphism may be used to predict risk of vitamin D deficiency.

Hyperhomocysteinemia is Associated with Inflammation, Bone Resorption, Vitamin B12 and Folate Deficiency and MTHFR C677T Polymorphism in Postmenopausal Women with Decreased Bone Mineral Density.

Osteoporosis is an age-related bone disease, affecting mainly postmenopausal women, characterized by decreased bone mineral density (BMD) and consequent risk of fractures. Homocysteine (Hcy), a sulfur-aminoacid whose serum level is regulated by methylenetrahydrofolate reductase (MTHFR) activity and vitamin B12 and folate as cofactors, is a risk factor for inflammatory diseases. Literature data concerning the link between Hcy and osteoporosis are still debated. The aim of our study was to assess the relationship among Hcy and BMD, inflammation, vitamin status and bone turnover in postmenopausal osteoporosis. In 252 postmenopausal women, BMD was measured by dual-energy X-ray absorptiometry (DXA). In addition to serum Hcy, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and bone turnover markers (bone alkaline phosphatase-BAP, osteocalcin-OC, C-terminal telopeptide of type I collagen (CTX), vitamin deficiencies and MTHFR-C677T polymorphism were evaluated. Hcy, inflammation, bone resorption markers and prevalence of C677T polymorphism were higher, whereas vitamin D, B12, folate, and bone formation markers were lower in women with decreased BMD compared to those with normal BMD. Our results suggest a significant association between Hcy, BMD and inflammation in postmenopausal osteoporosis. The regulation of Hcy overproduction and the modulation of the inflammatory substrate could represent additional therapeutic approaches for osteoporosis prevention.

TNF-α G-308A polymorphism in post-menopausal women with osteoporosis

TNF-α G-308A polymorphism in post-menopausal women with osteoporosis

Gene\u2013diet-related factors of hyperglycaemia in postmenopausal women

As ageing and increased body fat are the signs of insulin resistance, we have studied whether the presence of Pro12Ala and C1431T of peroxisome proliferator-activated receptor gamma 2 gene and Trp64Arg of beta 3-adrenergic receptor gene may predispose to the hyperglycaemia development in postmenopausal women, who have never undergone hypoglycaemic treatment. The distributions of selected allele and genotype frequencies were determined by the PCR–RFLP method in normo- and hyperglycaemic, who have never been diagnosed and treated for diabetes mellitus were measured. The amount of body fat and lean body mass (LBM) were assessed by the bioimpedance method and nutritional habits by 7-day dietary recall. There were no differences between the distribution of genotypes and the allele frequencies of the Pro12Ala, C1431T and Trp64Arg polymorphisms in normo- and hyperglycaemic women. Hyperglycaemic women were characterized by visceral obesity, hypertension, higher serum insulin and triglycerides, higher intake of fat and lower consumption of complex carbohydrates and B vitamins. Normoglycaemic women with Pro12Pro polymorphism acquired higher energy from dietary fat (p < 0.0276) and lower energy from carbohydrates (p < 0.0480) than normoglycaemic Ala12 carriers. Subjects with Pro12Pro polymorphism and LBM > 58% of total body mass or with Trp64Trp and normal triglycerides have higher chance of normoglycaemia. Genotyping for Pro12Ala and Trp64Arg polymorphism in postmenopausal women may have the clinical benefit of predicting hyperglycaemia, thereby contributing to the prevention of diabetes mellitus development in the future. However, not only the genetic background but also the dietary habits (intake of fat, carbohydrates and B vitamins) determine the risk of hyperglycaemia.

Macronutrient intakes and serum oestrogen, and interaction with polymorphisms in CYP19A1 and HSD17B1 genes: a cross-sectional study in postmenopausal Japanese women.

Although higher circulating levels of oestrogen are related to postmenopausal breast cancer risk, limited information is available regarding effects of diet on endogenous oestrogen. Thus, we examined associations between macronutrient intakes and serum oestrogen with consideration of polymorphisms in oestrogen-metabolising genes. In this cross-sectional study, 784 naturally menopaused Japanese women aged 47-69 years were selected from participants of the Japan Multi-Institutional Collaborative Cohort Study. We documented dietary intakes, measured serum concentrations of oestrone (E1) and oestradiol (E2) and genotyped polymorphisms in oestrogen-metabolising CYP19A1 (rs4441215 and rs936306) and HSD17B1 (rs605059) genes. Trends and interactions were examined using linear regression models. In addition, we calculated the ratios of the oestrogen concentrations of the second to the highest quartiles (Q2-Q4) of dietary intake to those of the lowest quartiles (Q1). After adjustment for potential confounders, E2 was significantly associated with intake of carbohydrate and noodles; ratios of Q4 v. Q1 were 1·15 (95 % CI 1·04, 1·28) and 1·15 (95 % CI 1·04, 1·26), respectively. In contrast, E2 levels were inversely associated with intake of total energy, SFA and n-3 highly unsaturated fatty acids (n-3 HUFA); ratios of Q4 v. Q1 were 0·90 (95 % CI 0·82, 0·99), 0·89 (95 % CI 0·81, 0·98) and 0·91 (95 % CI 0·83, 1·00), respectively. In stratified analysis by polymorphisms, the rs605059 genotype of HSD17B1 significantly modified associations of E2 with intake of n-3 HUFA and fish; the associations were limited to those with the CC genotype. Macronutrient intakes were associated with serum E2 level, and these associations may be modified by HSD17B1 polymorphism in postmenopausal women.

Searching for the relationship between the parameters of metabolic syndrome and the rs17782313 (T>C) polymorphism of the MC4R gene in postmenopausal women.

Metabolic syndrome (MS) is widespread in the human population, and its incidence is continuously increasing, generating serious health problems. The purpose of this study was to find the relationship between the parameters of MS and the melanocortin type 4 receptor (MC4R) gene polymorphism in postmenopausal women. The study involved 344 healthy Polish women, who had their last menstrual cycle 1 year ago or earlier. The study included blood analysis, survey, and body measurements. The mean age was 58.5±6.6 years. An increased body mass index was observed in 65.7% and abdominal obesity in 80.3% of the study population. MS was diagnosed in 40.7% of all participants, including 39.3% of women with the T/T genotype and 44.7% of those with the C/X genotype (χ2 test; P>0.05). A logistic regression model showed that the probability of MS was higher in patients with the C/X genotype (odds ratio =1.25) (χ2 test; P>0.05). The study concluded that MS is a very common condition among postmenopausal women. The C/X genotype of the MC4R gene seems to predispose postmenopausal women to developing some MS symptoms.

Cognitive Functions, Concentration of Endogenous Estradiol, Estrogen Receptor α (ERα) Polymorphism in Postmenopausal Women.

BackgroundThe goal of this study was to investigate the relationship between cognitive functions and the level of endogenous estradiol in postmenopausal women, according to which estrogen receptor α (ERα) polymorphism the woman carries.Material/MethodsThe study group consisted of 210 women. The inclusion criteria were: minimum 2 years after the last menstruation, FSH concentration 30 U/ml, and no dementia signs on Montreal Cognitive Assessment (MoCA). A computerized battery of Central Nervous System Vital Signs (CNS VS) test was used to diagnose cognitive functions. Genotyping of the ERα polymorphism was performed using a polymerase chain reaction and restriction enzymes (PCR-RFLP). Blood plasma was tested for FSH and estradiol (E2). Statistical analysis was performed using STATISTICA software.ResultsA relationship was confirmed between standard scores for 3 cognitive functions: general memory, verbal memory, and processing speed, and the XbaI polymorphism in the women in the study. In the group of women with genotype TT PvuII, significant positive relationships were observed between the concentration of E2 and the standard scores of 3 cognitive functions: general memory, verbal memory, and processing speed. In the group of women with genotype TC PvuII, significant negative correlations were found between the concentration of E2 and the standard scores of 4 cognitive functions: NCI, general memory, verbal memory, and processing speed.ConclusionsERα polymorphism exerted an effect on the interaction between the concentration of estradiol and the results for cognitive functions. The concentration of estradiol did not depend on Xba1 and PvuII polymorphisms. The results for cognitive functions depended on which Xba1 polymorphism the woman carried.

PS 02-78 THE ASSOCIATION BETWEEN ESTRADIOL AND ESR1 GENE POLYMORPHISM IN POSTMENOPAUSAL WOMEN WITH ARTERIAL HYPERTENSION AND TYPE 2 DIABETES MELLITUS

Objective: To determine associations between estradiol and ESR1 gene polymorphism in postmenopausal women with arterial hypertension and type 2 diabetes mellitus. Design and Method: The study included 137 women from Kharkiv region of Ukraine including patients with type 2 Diabetes Mellitus (T2DM) (1st group, n = 30), arterial hypertension (AH) of 2–3 degree (2nd group, n = 34), T2DM and AH of 2–3 degree (3rd group, n = 42) and 31 healthy volunteer (4th group). Serum levels of estradiol were evaluated by ELISA. Assays of estrogen receptor gene alpha (ESR1) were performed using restriction analysis of the amplification products of genome specific regions, i.e., promoter region T397C. Results: The levels of estradiol were the following in the studied patients: group 1 - (52.34 ± 1.15) pg/L, group 2 - (41.36 ± 1.16) pg/L, group 3 - (31.82 ± 1.69) pg/L and healthy volunteers - (55.30 ± 1.51)pg/L. Differences between group 1 and 2, 2 and 3, 1 and 3, patients with hypertension (groups 2 and 3 together) and healthy volunteers were significant (p < 0.05). Homozygote TT genotype of the ESR1 gene predominated in healthy donors 70.97 ± 8.15% (n = 22) compared to patients: group 1 - 10.00 ± 5.48% (n = 3), group 2 - 8.82 ± 4.86% (n = 3) and group 3 - 11.90 ± 5.00 (n = 5). Heterozygous TC genotype of the ESR1 gene was observed in 56.67 ± 9.05% (n = 17) of patients in group 1, 67.65 ± 8.02% (n = 23) in group 2, 61.90 ± 7.49% (n = 26) in group 3 and 12.90 ± 6.02% (n = 4) of healthy volunteers. Homozygous CC genotype of the ESR1 gene was found in 33.33 ± 8.61% (n = 10) of patients of group 1, 23.53 ± 7.27% (n = 8) in group 2, 26.19 ± 6.78% (n = 11) in group 3, and in 16.13 ± 6.61% (n = 5) of healthy volunteers. Differences between heterozygous TC genotype of the ESR1 gene in the 2nd and 3rd groups were significant (p < 0.05). Conclusions: Women with hypertension had significantly lower levels of serum estradiol than healthy female volunteers. This coincided with greater frequency of heterozygous TC polymorphism T397C of the ESR1 gene.

COGNITIVE CHANGES, ANDROGENS’ LEVEL AND APOLIPOPROTEIN E POLYMORPHISM IN POSTMENOPAUSAL WOMEN

COGNITIVE CHANGES, ANDROGENS’ LEVEL AND APOLIPOPROTEIN E POLYMORPHISM IN POSTMENOPAUSAL WOMEN

Interaction between C-reactive protein and cognitive functions according to APOE gene polymorphism in post-menopausal women.

IntroductionA potential factor increasing the risk of the development of cognitive impairment with age is apolipoprotein E (APOE) ε4 carrier status. A subsequent factor which may increase the risk of development of cognitive impairment at an older age is the concentration of C-reactive protein (CRP). The objective of the study was to examine the relationship between cognitive functions and the concentration of CRP in post-menopausal women who were carriers of particular apolipoprotein E gene (APOE) polymorphisms.Material and methodsA group of 402 women was recruited to the study. The inclusion criteria were: minimum two years after the last menstruation, follicle-stimulating hormone (FSH) concentration 30 U/ml, no dementi signs on Montreal Cognitive Assessment (MoCA). The computerized battery of the Central Nervous System Vital Signs (CNS VS) test was used to diagnose cognitive functions. APOE genotyping was performed by multiplex PCR. The blood plasma CRP levels were determined. Statistical analysis was performed using Statistica software.ResultsThe level of neurocognitive index (NCI) and cognitive functions in post-menopausal women depends on apolipoprotein E gene polymorphism (p < 0.001) and the concentration of CRP (p < 0.05). A negative correlation was found between CRP and NCI (p = 0.018), and the reaction time (p = 0.008) of women with APOE ε2/ε3. A positive correlation was observed between CRP and visual memory (p = 0.025) in women with APOE ε3/ε3, and verbal memory (p = 0.023) in women with APOE ε3/ε4 or ε4/ε4.ConclusionsApolipoprotein E gene polymorphism may modify the relationship between CRP concentration and cognitive functions in post-menopausal women.

Cognitive functions, lipid profile, and Apolipoprotein E gene polymorphism in postmenopausal women.

The objective of the study was investigation of the relationship between cognitive functions and lipid profile, BMI and change of body weight in postmenopausal women carriers of Apolipoprotein E gene polymorphisms (APOE). A group of 170 women was recruited to the study. The inclusion criteria were: minimum of two years after the last menstruation, FSH concentration 30 U/ml and no signs of dementia on the Montreal Cognitive Assessment (MoCA). A computerized battery of Central Nervous System Vital Signs (CNS VS) was used for diagnostic cognitive functions. APOE genotype was performed by multiplex PCR. In blood plasma were determined: triglycerides, total cholesterol and its fractions: HDL cholesterol and LDL cholesterol. Statistical analysis was performed using two-way analysis of variance in STATISTICA software. In the postmenopausal women examined, the carrier state of APOE gene polymorphism was associated with the level of triglycerides, and results concerning three cognitive functions: executive functions, psychomotor speed, and cognitive flexibility. Loss of body weight in postmenopausal women was related with lower results in neurocognitive index and the majority of cognitive functions. The results concerning cognitive functions in postmenopausal women in the study were not significantly related with lipid profile. Significant differences were observed according to APOE gene polymorphism in correlations between LDL/HDL and CHOL/HDL ratios, and results in the processing speed and reaction time, as well as between the BMI and results in processing speed in the postmenopausal women examined.

Association of Mannose-Binding Lectin 2 (mbl2) gene heterogeneity and its serum concentration with osteoporosis in postmenopausal women

The aim of the study was to detect prevalence of MBL2 exon 1 (codons 52, 54 and 57) genetic polymorphism in postmenopausal women in Bosnia and Herzegovina and its possible role as genetic risk factor for susceptibility to occurrence of osteoporosis in this study group. Also, we investigated association between MBL serum concentrations and osteoporosis in postmenopausal women. Genetic codons' variations were determined by PCR-RFLP and MBL in serum was measured by ELISA method in 75 postmenopausal women (37 with osteoporosis and 38 apparently healthy, non-osteoporotic women serving as a control). Serum MBL levels were not significantly different between osteoporosis and control group (492 (37-565.1) and 522.6 (477-559.4) ng/mL respectively, p=0.206). Genotype frequencies were not significantly different (p=0.997) between the studied groups of postmenopausal women. Genotype frequencies A/A, A/0 and 0/0 in osteoporosis group were 0.576; 0.405; 0.018 and in control group 0.562; 0.412; 0.026, respectively. Frequencies of A and 0 allele were 0.78 and 0.22 in osteoporosis and 0.77 and 0.23 in control group. The results do not suggest association of functional polymorphism of MBL2 gene and MBL serum concentration with osteoporosis in postmenopausal females.

Bone mineral density, carotid artery intima-media thickness, and Klotho gene polymorphism in postmenopausal women

Abstract

The 8-hydroxydeoxyguanosine concentrations according to hormone therapy and S326C polymorphism of OGG1 gene in postmenopausal women

BackgroundThe 8-hydroxydeoxyguanosine (8-OHdG) is widely used for determination of DNA damage since it is excised from oxidative damaged DNA with endonuclease repair enzymes coded by 8-oxoguanine DNA N-glycosylase gene (OGG1). The present study aimed at investigating whether hormone therapy (HT) may influence on the blood/urinary 8-OHdG levels and whether the level of 8-OHdG is different according to OGG1 S326C polymorphism in postmenopausal women receiving HT. MethodsIn 102 postmenopausal women receiving HT, the 8-OHdG levels were measured in the blood and urine using high performance liquid chromatography (HPLC) before HT and 3months after HT. The genotyping of the S326C polymorphism of the OGG1 was performed by polymerase chain reaction (PCR) and restriction enzyme fragment length polymorphism (RFLP) analysis. ResultsAfter HT, mean blood 8-OHdG level significantly decreased compared to those before HT (P=0.003), while urinary 8-OHdG level did not show any difference according to HT. Pre-HT level of 8-OHdG was not different according to OGG1 genotypes and similar finding was demonstrated in post-HT 8-OHdG concentration. ConclusionsThese findings imply that hormone therapy can reduce blood 8-OHdG concentration, one of the markers of oxidative damage. Further study is needed to confirm this association in larger population.

Association of interleukin-1 beta (-511C/T) polymorphisms with osteoporosis in postmenopausal women

BACKGROUND AND OBJECTIVES:Osteoporosis is a common disease of the elderly, in which genetic and clinical factors contribute to the disease phenotype. Since the production of interleukin-1 (IL-1) has been implicated in the bone mass and skeletal disorders, we investigated whether IL-1 system gene polymorphisms are associated with the pathogenesis of osteoporosis in postmenopausal Taiwanese women.METHODS:Osteoporosis is diagnosed by dual-energy x-ray absorptiometry, which measures bone mineral density (BMD) at multiple skeletal sites. We studied the IL-1α (-889C/T), IL-1β (-511C/T) and the 86 base pair variable number tandem repeat (VNTR) in intron 2 of the IL-1 receptor antagonist (IL-1ra) gene in 117 postmenopausal women with osteoporosis and 135 control subjects without a history of symptomatic osteoporosis. These gene polymorphisms were analyzed by polymerase chain reaction and restriction fragment length polymerase. Blood sugar and other risk factors were also determined.RESULTS:The frequencies of IL-1β (-511C/T) genotypes (P=.022, odds ratio=1.972) and alleles (P=.02, odds ratio=2.909) showed a statistically significant difference between the two groups. However, we did not find any statistically significant difference in IL-1α and IL-1ra polymorphisms (P>.05). We also observed a positive relationship between osteoporosis and cholesterol and a weak inverse relationship between blood sugar and osteoporosis in postmenopausal women.CONCLUSIONS:These experimental results suggest that the pathogenesis of osteoporosis is associated with IL-1β (-511C/T) polymorphism in postmenopausal women. This polymorphism is an independent risk factor for osteoporosis.

Association between androgen receptor gene polymorphism and bone density in older women using hormone replacement therapy

Objective The objective of this study was to investigate the relationship between bone mineral density (BMD) and both CAG repeat polymorphism of the androgen receptor (AR) gene and skewed X chromosome inactivation (SI) in postmenopausal women. Methods BMD was measured by DEXA. Both the number and the X-weighted biallelic mean of the CAG repeats of AR were analysed by PCR, before and after DNA digestion with methylation-sensitive HpaII in 192 healthy Caucasian postmenopausal women. Results The number of CAG repeats ranged from 10 to 34, with a median value of 22. CAG) n≤22 and CAG) n≥23 alleles were designated as short and long alleles, respectively. In women using hormone replacement therapy (HRT) ( n = 81), lumbar spine BMD was significantly lower, and femoral neck and total body BMD marginally lower in those with long-long alleles when compared with those with other genotypes. SI (≥80%) was observed in 24% of the women and was not associated with BMD. In women using HRT, femoral neck BMD was significantly lower, and lumbar spine and total body BMD marginally lower in those whose X-weighted CAG repeat biallelic was greater than 22.59 (median value) when compared to other genotypes. These results were not found in women not using HRT. Conclusion In conclusion, our results suggest that BMD may be associated with AR gene polymorphism in postmenopausal women using HRT but not with SI. Further studies are needed to investigate the mechanisms of the interaction between HRT, BMD and AR found in the present study.

Effects of estrogen-only therapy on LDL oxidation in women with hysterectomy: Does paraoxonase genotype play a role?

Objectives This study investigated the effects of estrogen-only therapy on lipid profile (through susceptibility of low density lipoproteins to oxidation) and on oxidant-antioxidant parameters in surgical menopausal women. PON genotypes are also evaluated considering that they may be associated with the personal differences observed in antioxidant effects induced by estrogen. Methods Thirty women who had undergone hysterectomy + bilateral ovariectomy in the last 3 years, with causes other than malignancy were included and given estrogen-only (Premarin-Wyeth Inc. 0.625 mg/day/6 months, equine conjugated estrogen). Blood samples were collected at baseline, first and sixth month of treatment. Serum (total antioxidant activity-TAO and PON activity), erythrocyte (TBARS and catalase activity), LDL and Cu 2+ induced ox-LDL (TBARS and diene levels) samples were evaluated and PON1 192 polymorphisms were determined by PCR amplification & restriction enzyme digestion. Results At the sixth month, a higher TAO activity ( p = 0.016) and a lower eTBARS ( p = 0.028) were detected compared to the basal values. LDL and Cu induced ox-LDL TBARS levels at the sixth month of treatment were significantly ( p = 0.012 and 0.026, respectively) lower compared to the pretreatment values. Baseline eTBARS ( p = 0.007), LDL TBARS ( p = 0.044) and eCAT ( p = 0.033) activities were significantly higher in homozygote Q allele carriers compared to subjects with R allele. LDL TBARS and Cu 2+ induced ox-LDLTBARS of QQ subjects ( p = 0.018 and 0.050) as well as LDL TBARS of QR subjects ( p = 0.044) showed a significant decrease with estrogen-only treatment. Conclusions Our study drives the attention to PON polymorphism in postmenopausal women who have risk for atherosclerosis. Although our data is limited, this study is the first that focuses on the role of PON genotypes in antiatherosclerotic effects of estrogen-only and provides important points for further studies.

Bone mass effects of a BMP4 gene polymorphism in postmenopausal women

The pathogenesis of osteoporosis involves both genetic and environmental factors. On the basis of linkage data suggesting gene effects on bone density at chromosome 14q and data locating the BMP4 gene to 14q, we performed a positional candidate study to examine a possible association of BMP4 gene polymorphisms, hip bone density ( n = 1012) and fracture rates ( n = 1232) in postmenopausal women (mean age 75). On genotype analysis of the three selected single nucleotide polymorphisms (SNP), the 6007C > T polymorphism was associated with total and intertrochanteric hip BMD and BMD was lower in the 32% of subjects homozygous for the C allele. This polymorphism codes for a nonsynonymous amino acid change with the T allele coding for valine, while the C allele codes for alanine. The difference in BMD was 3.1% (TT vs. CC) and 2.3% (CT versus CC) for the total hip ( P = 0.023), and 3.7% (TT vs. CC) and 2.8% (CT versus CC) for the intertrochanter site ( P = 0.012). Haplotype analysis demonstrated 6 haplotypes of frequency greater than 2%. A major haplotype defined by G-C-T alleles in SNPs −5826G > A, 3564C > T and 6007C > T respectively, showed association with high bone mass. No SNP showed association with fracture rates. We conclude that a polymorphism found in the BMP4 gene, affecting amino acid sequence, is associated with hip bone density in postmenopausal women, presumably via regulation of anabolic effects on the skeleton.