PvuII Polymorphisms Research Articles

P95 MRAS – A STRONG CANDIDATE GENE (SCG) FOR CORONARY ARTERY DISEASE (CAD)

The possible association of genetic markers at the apolipoprotein E (HhaI polymorphism), apolipoprotein B (XbaI, EcoRI and Ins/Del polymorphisms), and low-density lipoprotein receptor (LDLR) (AvaII, HincII and PvuII polymorphisms) with coronary artery disease (CAD) was evaluated in 50 Brazilian women with CAD diagnosed by angiography and in 100 healthy women (controls). The frequency of E3/E4 genotype for HhaI polymorphism at the Apo E gene was significantly higher in CAD patients than in controls (40% vs. 14%, respectively, P<0.001). Similarly, the X−X− genotype for XbaI polymorphism was more frequent in CAD individuals than controls (42% vs. 12%, P<0.0001). The A+A+ and P1P1 genotypes for AvaII and PvuII polymorphisms at the LDLR locus were also higher in CAD subjects than controls (44% vs. 16%, P<0.001 and 64% vs. 39%, P<0.05, respectively). The estimated relative risks for CAD in women carrying the E3/E4, X−X−, A+A+ and P1P1 genotypes were 4.1 [95% confidence interval (CI), 3.0–5.6], 5.3 (95% CI, 3.8–7.5), 4.1 (95% CI, 3.0–5.5), and 2.8 (95% CI, 2.2–3.6), respectively. This study demonstrates that Apo E, Apo B and LDLR gene polymorphisms are associated with CAD in Brazilian Caucasian women.

Genotypes and Haplotypes of the Estrogen Receptor Genes, but Not the Retinoblastoma-interacting Zinc Finger Protein 1 Gene, Are Associated with Osteoporosis

Osteoporosis is a common age-related disease with a strong genetic influence. Polymorphisms of ESR1 have consistently been shown to be associated with bone mineral density (BMD) and fracture; however, in regulating bone metabolism, ESR1 interacts with both ESR2 and RIZ1. We therefore examined the effects of polymorphisms in the ESR1, ESR2, and RIZ1 genes and their haplotypes on vertebral fractures and BMD in a case-control study comprising 462 osteoporotic patients and 336 controls. In ESR1, we found the variant C allele of the XbaI polymorphism to be associated with decreased risk of vertebral fractures in women (P < 0.01), whereas in men, the T allele seemed protective (P = 0.05). The variant G allele of the PvuII polymorphism decreased the risk of vertebral fractures independently of lumbar spine BMD in women (P = 0.04) but had no effect in men. Haplotype X-P-H (XbaI:C, PvuII:G, and a high number of TA repeats) was associated with decreased risk of vertebral fractures in women (P = 0.04) but not men. In ESR2, the G allele of the AluI polymorphism was associated with increased fracture risk (P = 0.04), and the haplotype that comprises rs1256031:T and AluI:A increased lumbar spine BMD by 0.04 +/- 0.02 g/cm(2) (P < 0.05) and decreased the risk of vertebral fractures (P = 0.04). There was no effect of the RIZ1 polymorphism on BMD or fracture risk and no evidence of interaction between the polymorphisms and haplotypes thereof. We confirm that genetic variants in ESR1 and ESR2, but not RIZ1, are important in osteoporosis. We found no evidence of interaction between polymorphisms, but we found that the effects of genetic variants in ESR1 might be sex dependent.

Pharmacogenetics of tamoxifen in relation to disease-free survival in a Dutch cohort of the tamoxifen exemestane adjuvant multinational (TEAM) trial.

510 Background: Retrospective studies on the relationship between CYP2D6 genotype and tamoxifen efficacy show conflicting results (Dezentje et al., Clin Cancer Res 2009:15;15-21). Negative studies have been criticized because of heterogeneous populations, lack of controlling for possible confounders and of systematic documentation of treatment adherence and outcome measures. Well documented studies on homogeneous populations with a more comprehensive pathway approach are imperative. Methods: 747 Dutch patients who were randomized to receive tamoxifen followed by exemestane after 2.5 to 3 years within the TEAM Trial were genotyped for 29 germline genetic variants in 12 candidate genes encoding enzymes that are involved in the metabolic and pharmacodynamic pathway of tamoxifen. These variants were related to disease free survival (DFS) during tamoxifen use (censored at the time of switch to exemestane). A multivariable Cox regression was used to adjust for clinically relevant factors. Results: The clinical characteristics of the genotyped patients were similar to the entire Dutch TEAM cohort randomized to tamoxifen (n = 1,379). DFS was associated with UGT2B15*2 [Vt/Vt + Wt/Vt vs. Wt/Wt: HR = 0.51 (0.27-0.95); p = 0.034] and the estrogen receptor-1 polymorphism ESR1 PvuII [gene-dose effect: HR = 1.72 (1.10-2.69); p = 0.017]. In the univariable analysis CYP2C19*2 was associated with DFS [Vt/Vt vs Wt/Vt + Wt/Wt: HR = 3.85 (1.64-9.05); p = 0.002]. However, this association lost significance when adjusted for the ESR1 PvuII polymorphism. No association was found between the CYP2D6 genotypes and DFS. Conclusions: This translational study suggests that common and therefore relevant polymorphisms in UGT2B15 and the estrogen receptor-1 impact DFS in breast cancer patients treated with adjuvant tamoxifen. The previously reported association between CYP2D6 genotype and tamoxifen efficacy was not confirmed in our study. No significant financial relationships to disclose.

Height at menarche is influenced by estrogen receptor α gene polymorphisms

It has been suggested that polymorphic variations in estrogen receptors (ERs) genes may have an impact on linear growth of girls during puberty. The aim of the study was to investigate whether height at menarche is influenced by PvuII and XbaI polymorphisms of the ERalpha gene. The study population consisted of 127 healthy girls, who were observed from premenarcheal period at six monthly intervals, until menarche occurred in all participants. Anthropometric measurements were taken at each visit and their values at menarche were calculated using centile curves drawn individually for each subject. PvuII and XbaI ERalpha gene polymorphisms were evaluated with RLFP-PCR. The age at menarche was not related to ERalpha gene polymorphisms. Girls with pp genotype were at menarche on average 3.2 cm shorter than PP homozygotes and in addition xx homozygotes were shorter than subjects with XX and Xx genotypes: 3.0 cm and 3.9 cm respectively. Subjects with px haplotype were, at the onset of the first menstrual period, from 2.3 cm to 3.1 cm shorter than carriers of other haplotypes. The leg length-to-height ratio at menarche was lower in xx homozygotes than in Xx heterozygotes and lower in px haplotype in comparison to Px and pX haplotypes carriers. Corresponding associations were observed at the final visit. Height at menarche is influenced by the ERalpha gene polymorphism.

Association analysis of genetic polymorphisms and potential interaction of the osteocalcin (BGP) and ER-α genes with body mass index (BMI) in premenopausal Chinese women

To investigate whether estrogen receptor alpha (ER-alpha) PvuII and osteocalcin (also known as bone Gla protein, or BGP) HindIII genetic polymorphisms and their potential interactions are associated with body mass index (BMI) variation. Data on BMI and ER-alpha PvuII and BGP HindIII genotypes were obtained from 328 healthy premenopausal Chinese women in east China. The study subjects were unrelated, at least 21 years old (mean age of 33.2+/-5.9 years), and had an average BMI of 21.58+/-2.59. All subjects were genotyped at the ER-alpha PvuII and BGP HindIII loci using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). The BGP HindIII genotypes were significantly associated with BMI (P=0.003). Carriers of the HH and Hh genotypes had approximately 2.73% and 1.27% higher BMI than those of the hh genotype, respectively. In contrast, the ER-alpha PvuII polymorphism was not significantly associated with BMI (P=0.454). In addition, there was no evidence of potential interactions between the ER-alpha and BGP genes in our subjects (P>or=0.013). The HindIII polymorphism of the BGP gene, but not the PvuII polymorphism of the ER-alpha gene or their potential interaction, was associated with BMI in premenopausal Chinese women.

Estrogen Receptor-1 Genetic Polymorphisms for the Risk of Premature Ovarian Failure and Early Menopause

The aim of this study was to investigate the role of the estrogen receptor 1 (ESR1) genetic polymorphisms for early menopause that was classified as premature ovarian failure (POF) and early menopause (EM) and to examine whether the associations of ESR1 genetic variants are different for POF and EM. We selected 100 POF cases and matched 100 EM cases and 200 normal menopause (NM) controls from the Korean Multi-Center Cohort. Among them, we restricted idiopathic POF and EM cases vs NM controls by excluding POF/EM cases with medical/surgical causes. The XbaI (rs9340799) and PvuII (rs2234693) in the ESR1 gene were genotyped. The single-nucleotide polymorphism (SNP) and haplotype effects were analyzed by multivariate logistic regression and haplotype analysis. Also nominal polytomous logistic regression was used to find whether ESR1 genetic variants are differently associated with POF and EM. The global p values for idiopathic POF and EM were 0.08 and 0.39 (SNP-based), and <0.001 and 0.12 (haplotype-based), respectively. The XbaI genetic variant containing the X allele was marginally significantly associated with a reduced risk of idiopathic POF (OR = 0.6, 95% CI 0.3-1.0). The P-x haplotype and diplotypes significantly decreased the risk of idiopathic POF (OR = 0.5, 95% CI 0.2-0.9; OR = 0.4, 95% CI 0.2-0.9, respectively). In contrast from POF, the P-x haplotypes and diplotypes insignificantly increased the risk for both idiopathic EM (p(polytomous) = 0.009 for P-x haplotype; p(polytomous) = 0.02 for P-x diplotypes). Our results suggest that the ESR1 gene including PvuII and XbaI polymorphisms may modify the risk of idiopathic premature ovarian failure (POF) but not idiopathic early menopause (EM) risk.

Association of estrogen receptor-α gene polymorphisms with cardiac autonomic nervous activity in healthy young Japanese males

Background Estrogens exert beneficial effects on the cardiovascular system that are mediated by estrogen receptors. We examined the association between the estrogen receptor α gene ( ESR1) PvuII and XbaI polymorphisms and cardiac autonomic nervous function in Japanese males. Methods We examined 252 young healthy males for association of ESR1 PvuII and XbaI polymorphisms and short-term heart rate variability (HRV) during supine rest and in a standing position. The very low frequency (VLF), low frequency (LF), and high frequency (HF) components of HRV were quantified by frequency domain analysis. Results Carriers of the ESR1 PvuII C allele had higher mean blood pressure (BP), while the XbaI GG genotype was significantly associated with higher diastolic and mean BP, but lower HR. In the haplotype analysis, carriers of the ESR1 haplotype 2 ( PvuII C and XbaI A) allele had a higher systolic and mean BP, and lower HRV spectral powers (total power, VLF, LF, and HF components) in a supine rest compared with those of non-carriers. Conclusions The ESR1 PvuII and XbaI haplotype is associated with BP variation and the reduction in cardiac autonomic nervous activity in young Japanese males, which may be precursors of future pathological episodes of cardiovascular diseases.

Association of Estrogen Receptor-Alpha Gene Polymorphism with Pathogenesis of Osteoporosis in Korean Vegetarian Men

Objective: The purpose of this study was to investigate the association between two genetic polymorphisms (PvuII and XbaI restriction fragment length polymorphisms, RFLPs) of the estrogen receptor-α (ER1) gene and the quantitative ultrasound (QUS) parameters at the calcaneus. Subjects and Methods: Two hundred and sixty-six Korean vegetarian men, mean age 50.9 ± 12.0 years (range 26–80), were studied. Polymorphisms at the ER1 gene sites and the cross-sectional associates of genetic factors with calcaneal QUS parameters including broadband ultrasound attenuation (BUA) and the speed of sound (SOS) were analyzed by RFLPs using polymerase chain reaction. Results: The distribution of PvuII and XbaI RFLPs in the ER1 gene was as follows: PP 11.6%, Pp 47.2%, pp 41.2%, XX 1.2%, Xx 24.4% and xx 74.4%. After adjusting for potential confounding factors such as age and body mass index, two genetic polymorphisms of the ER1 gene were independently associated with BUA, SOS and stiffness index at the calcaneus of our subjects. The QUS measurements of the subjects with the xx genotype were higher than those of the subjects with an Xx genotype, while the QUS measurements of the subjects with a Pp genotype were significantly lower than those of the subjects with PP or pp genotypes (p < 0.05). Conclusion: The results suggest that the PvuII and XbaI RFLPs of the ER1 gene may be genetic factors that affect QUS at the calcaneus.

Association between Estrogen Receptor Gene Polymorphisms and Depression in Post-Menopausal Women: A Preliminary Study

Post-menopausal women experience variable biological and psychological changes. The effect of reduced levels of estrogen can effect on post-menopausal depression. Estrogen triggers physiological responses by binding to the estrogen receptor (ER). Two subtypes of ER, ERa and ERb are now known. We investigated the significance of ERa and ERb polymorphisms and post-menopasal depression in this study. Forty three women with post-menopausal depression and 63 post-menopausal women without depression as normal controls were recruited. Polymerase chain reaction-restriction fragment length polymorphism method was used to investigate genotypes of ERa and ERb polymorphisms. Genotypes of PvuII and XbaI polymorphism of ERa receptor were significantly different in patients with post-menopausal depression comparing with controls. Genotypes of ERb did not show association with post-menopausal depression. Our study showed that ERa receptor polymorphism had an association with depression in post-menopausal women. It suggests that investigation of ER genes and their functions might be important for understanding pathophysilogical mechanism of post-menopausal depression.

Association of Estrogen Receptor-α Gene PvuII Polymorphisms with the Effect of Calcium Supplementation on Skeletal Development in Chinese Pubertal Girls

To investigate the association of estrogen receptor alpha (ER-alpha) PvuII polymorphisms with the effect of calcium supplementation on bone development in Chinese pubertal girls, and to study the importance of calcium supplementation by maximizing the peak bone mass at their pubertal stage for bone development and osteoporosis prevention and the role of estrogen in regulating bone mass. Ninety-four pubertal girls were recruited in the study and divided into two groups and three sub-groups according to the ER-alpha PvuII polymorphisms. One year before and after calcium supplementation, bone mineral density (BMD) was measured by DEXA, while BGP, BAP, TRACP5b, and 25-OH-VitD(3), as well as estrogen were detected by ELISA. Analysis of covariance was used to examine the effect of ER-alpha polymorphisms on bone development. The absolute increase and percentage change of BGP were significantly higher in the supplemented group than in the control group (P<0.05). In the intervened group, The increase and percentage change of the total body and radio distal 1/3 BMD were higher in PP than in PP genotype (P<0.05), and the increase of BAP in Pp was also higher than PP in the same group (P<0.05). PP genotype shows a better response to calcium supplementation than the other PvuII polymorphisms.

Role of genetic polymorphism of estrogen receptor-α gene and risk of prostate cancer in north Indian population

Present study depicted the role of polymorphisms in estrogen receptor-alpha gene in association with prostate cancer in north Indian population. The study was performed on 157 cases of prostate cancer, 170 cases of BPH, and 170 healthy Indian males diagnosed with prostate cancer and benign prostatic hyperplasia (BPH) and healthy males as controls. Determination of polymorphism in the ER-alpha gene was done by polymerase chain reaction followed by restriction fragment length polymorphism (RFLP) analysis with PvuII and XbaI enzymes. An association was observed between PvuII polymorphism of ER-alpha gene and that of prostate cancer. However, there was no such association with XbaI polymorphism in ER-alpha gene.

Estrogen receptor gene polymorphisms in patients with idiopathic premature ovarian failure

It has been reported that polymorphisms in the estrogen receptor (ER)-alpha gene (ESR1) may be associated with reproductive patterns of women. This study was performed to investigate whether the genetic polymorphisms of the ER-alpha gene are associated with idiopathic premature ovarian failure (POF) in a Korean population. The subjects were 126 idiopathic POF patients and 221 post-menopausal controls recruited from university hospitals between 1999 and 2004. Genotyping was performed by MGB primer/probe Taqman assay. Haplotypes were deduced by using the Haploview version 4.1. Bonferroni correction was applied for the correction of multiple testing. There was no significant difference in the allele distribution of the ER-alpha gene (TA)n repeats between the POF and the control group. For the PvuII polymorphism, the POF group showed a higher frequency of TT genotype compared with the controls (41.3 versus 26.3%, P = 0.004, 98.75% CI 1.8-28.2%). No significant difference was found in the distribution of the XbaI polymorphism between the POF and the control group. Haplotype analysis showed that the frequency of TA haplotype was significantly higher in the POF patients compared with the controls (64.7 versus 52.7%, P = 0.002, 98.75% CI 2.4-21.6%). These findings suggest that the ER-alpha gene polymorphisms may be associated with idiopathic POF.

Assessment of association of estrogen receptor-α gene polymorphism with physical activity and bone metabolism

Genetic and environmental factors have long been suspected to influence on athletic performance and bone metabolism. We have therefore investigated a population-based association study of Korean elite athletes relative to the general population with PvuII polymorphism of the ER-α gene. In addition, interactions between the ER-a genotype distribution and variation of biochemical parameters for bone metabolism during short-duration aerobic performance development were analyzed in a Korean middle-aged women population. The ER-a gene locus was found to be deviation from Hardy-Weinberg equilibrium (p<0.05), but not in the female athlete group. The most common ER-α genotype wasPp in elite athletes (44/72) and controls (74/109), with higher than expected number of heterozygotes (p<0.05). No statistically significant difference in the distribution of ER-a genotype frequency was observed between the elite athletes and control groups. In contrast, almost all biochemical markers studied here appeared to be significantly higher levels after 12-week exercise training compared with baseline in both groups of Korean women, although there was no genotype effect on the change of levels of the bone metabolic parameters. Thus, our data imply that regularly exercise training may affect bone metabolism, but the genetic marker of ER-a gene polymorphism may not be valuable indicator for the development of elite athletes and physical therapy educational program.

Oestrogen receptor alpha gene intronic polymorphisms and autoimmune myasthenia gravis in Caucasian women

Autoimmune myasthenia gravis is a disorder with a complex pathomechanism in which sex hormones, in particular oestrogen, have long been considered to play a role. Here we report the result of a case-control study which evaluated the association of two oestrogen receptor alpha gene polymorphisms with myasthenia gravis in Caucasian patients. PvuII (rs2234693) and XbaI (rs9340799) restriction fragment polymorphisms of the oestrogen receptor alpha gene were analyzed in 113 female myasthenia patients and 184 female controls. Distribution of these polymorphisms was compared with PCR-RFLP. Patients were divided into groups according to their oestrogen receptor alpha genotypes, and acetylcholine receptor antibody status and age of onset were compared between the groups. We found no significant difference between any of the groups implying that these two polymorphisms probably do not play a role in the pathomechanism of myasthenia gravis in Caucasian women.

Role of the oestrogen receptor (ESR1 PvuII and ESR1 325 C→G) and progesterone receptor (PROGINS) polymorphisms in genetic susceptibility to migraine in a North Indian population

We aimed to explore the single-locus, haplotype and epistasis patterns and the contribution of oestrogen receptor [ESR1 PvuII (rs2234693), ESR1 325 C→G (rs1801132)] and progesterone receptor [PROGINS (rs1042838)] polymorphisms in genetic susceptibility to migraine by analysing 613 subjects consisting of 217 migraine patients, 217 healthy controls (HC) and 179 patients with tension-type headache (TTH). Entire data were analysed by taking the Bonferroni corrected P-value into account. We found significant association of TT genotype [odds ratio (OR) 3.458, confidence interval (CI) 1.757, 6.806; P = 0.0003] and T allele (OR 1.729, CI 1.309, 2.284; P = 0.0001) of ESR1 PvuII single nucleotide polymorphism with migraine when compared with HC. Significant association was seen only in female migraine patients at both genotype (P = 0.002; OR 3.834, CI 1.625, 9.043) and allele level (P = 0.002; OR 1.721, CI 1.228, 2.413). Moreover, higher risk was limited to migraine with aura (MA) (in case of TT genotype, P = 0.002; OR 4.377, CI 1.703, 1.246; in case of T allele, P = 0.001; OR 1.888, CI 1.305, 2.735) rather than migraine without aura (MoA) (P-value of TT genotype = 0.003; OR 3.082, CI 1.465, 6.483; P-value T allele = 0.002; OR 1.630, CI 1.188, 2.236). In case of a recessive model, risk was seen with migraine patients (P = 0.0003; OR 2.514, CI 1.635, 3.867), MA (P = 0.0001; OR 3.583, CI 1.858, 6.909) and MoA patients (P = 0.002; OR 2.125, CI 1.304, 3.464) when compared with HC. No risk was observed when TTH patients were compared with HC. No significance of ESR 325 G→C polymorphism was seen in any of the models under study. Significant differences in genotypic (P = 0.0001) and allelic frequency (P = 0.0002) were seen in case of PROGINS polymorphism when migraine patients were compared with HC, showing a protective effect (for A1A2 genotype, OR 0.292, CI 0.155, 0.549; for A2 allele, OR 0.320, CI 0.174, 0.589). Moreover, significance was seen only in case of female migraine patients at genotype (P = 0.002; OR 0.344, CI 0.176, 0.684) as well as allele levels (P = 0.004; OR 0.379, CI 0.198, 0.727) in case of PROGINS polymorphism. ESR1 PvuII TT*ESR1 325 C→G CG genotype, PROGINS A1A2*ESR1 325 C→G CG genotype and ESR1 PvuII CT*PROGINS A1A2 interacted significantly, but significance was lost after Bonferroni correction. In conclusion, ESR1 PvuII polymorphism is a significant risk factor for migraine particularly in women and MA patients, but ESR 325 C→G polymorphism is not associated with migraine susceptibility. PROGINS polymorphism seems to play a protective role in genetic susceptibility to migraine in the North Indian population.

Estrogen receptor α gene polymorphisms in patients with idiopathic premature ovarian failure

OBJECTIVE: It has been reported that polymorphisms in the ER-α gene (ESR1) may be associated with reproductive patterns of women. This study was performed to investigate whether the genetic polymorphisms of the ER-α are associated with idiopathic premature ovarian failure (POF) in a Korean population. DESIGN: Case-control study MATERIALS AND METHODS: The subjects consisted of 126 patients with idiopathic POF and 221 postmenopausal healthy controls. Genotyping of the PvuII and XbaI polymorphisms in the ER-α gene was performed by real-time polymerase chain reaction (PCR) analysis and TA dinucleotide repeat polymorphism was assessed by fluorescent PCR. Haplotypes were deduced by using the Haploview version 4.1. RESULTS: There was a significantly higher incidence of alleles with shorter (TA)n repeats (12-15 repeats) in the POF patients compared to the control group (59.9% vs. 50.9%, p = 0.022). For the PvuII polymorphism, the POF group showed a higher incidence of TT genotype compared with the controls (41.3% vs. 26.3%, p = 0.007). No significant difference was found in the genotype distributions or allele frequencies of the XbaI polymorphism between the POF and the control group. Haplotype analysis showed that the incidence of TA haplotype was significantly higher in the POF patients compared with the controls (64.7% vs. 52.7%, p = 0.002). CONCLUSIONS: These findings suggest that the ER-α gene polymorphisms may be associated with idiopathic POF.

Lipid profile and inflammatory markers associated with estrogen receptor α PvuII and XbaI gene polymorphisms

Estrogen is established to influence lipoprotein metabolism and inflammatory markers. Alternations in estrogen receptor alpha (ESR1) expression and function may affect the role of estrogen in this regard. The aim of this study was to determine whether ESR1 PvuII and XbaI gene polymorphisms have effects on lipoprotein (a) as well as inflammatory variables in an Iranian population. Three hundred and ninety seven consecutive participants (228 men, 57.4%) who were admitted at our center for elective coronary angiography because of symptoms related to coronary artery disease (CAD) were enrolled in our study. Total cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglyceride levels were determined by standard methods using commercial kits. Low-density lipoprotein (LDL)-cholesterol was calculated according to the Friedewald formula. The lipoprotein (a) levels were measured by ELISA method using Biopool kit, and the CRP concentrations were determined by Latex Immunoturbidometry. The presence of PvuII and XbaI polymorphisms within the ESR gene were analyzed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). The frequency of homozygous and heterozygous were 25.9% and 50.1%, for PvuII genotypes, and the frequency was 23.7% and 48.6%, for XbaI genotypes, respectively. After adjusting for CAD and age, no impacts of ESR1 PvuII and XbaI polymorphisms were found on lipid profile, lipoprotein (a) level, and quantitative CRP either in total population or in subgroups stratified by gender. In conclusion, our data demonstrate that ESR1 PvuII and XbaI gene polymorphisms did not seem to have an effect on lipoprotein metabolism or on inflammatory variables such as CRP.

Association of oestrogen receptor gene polymorphism with the long-term results of rotational acetabular osteotomy

Acetabular dysplasia (AD) contributes to the development of osteoarthritis of the hip. A rotational acetabular osteotomy (RAO) is one of the methods of pelvic osteotomy to prevent or treat secondary osteoarthritis of the hip. Although most of the patients that undergo RAO show satisfactory results, some have poor results. This study investigated whether gene polymorphisms of both the vitamin D receptor (VDR) and oestrogen receptor (ER) are involved in both AD and the postoperative results following RAOs. Sixty-four Japanese patients with AD who were treated by an RAO were enrolled in this study (59 women and 5 men, aged 13-59, with an average age of 40.3). Gene polymorphisms of the VDR [ApaI and TaqI restriction fragment length polymorphisms (RFLPs)] and ER (PvuII and XbaI RFLPs) were determined in these patients. The relationship between both the AD and radiographic postoperative changes of the hip joint after an RAO with these gene polymorphisms were examined. The frequencies of ER gene polymorphism coded as pp (RFLP/PvuII) in patients with AD were statistically significantly different (p = .011) from those coded as both PP and Pp. The joint space width narrowed even after RAO in 90% of the patients with the pp gene polymorphism, while it narrowed in only 35% of the patients with either PP or Pp seven years or longer after an RAO. The PvuII polymorphism in the ER gene was associated with the postoperative result of an RAO, while no association was observed between the AD with VDR and ER gene polymorphisms.

Association between estrogen receptor α gene polymorphisms and early restenosis after eversion carotid endarterectomy and carotid stenting

ObjectiveOur aim was to identify the role of PvuII and XbaI polymorphisms of the ESR1 (estrogen receptor alpha) gene in the occurrence of early restenosis after carotid endarterectomy and carotid artery stenting. MethodsIn a non-randomized prospective study we analysed blood samples from 172 patients (105 men) with severe stenosis of the internal carotid artery, using the PCR-RFLP method. Patients were treated either by carotid endarterectomy (n=82) or carotid artery stenting (n=90), and were followed-up by ultrasonography with a median follow-up time of 12 months (7.32–14.65 months). Conventional laboratory parameters were also recorded. Restenosis (>50%) rates were compared between patients carrying different genotypes and risk factors were calculated by using multivariate logistic regression. ResultsAllelic frequencies were similar between sexes (C/T allele, 0.40/0.60 and 0.43/0.57; p=0.67; G/A allele, 0.35/0.65 and 0.32/0.68; p=0.65; in men and women, respectively). Significantly higher restenosis rate was observed in patients homozygous for the A-allele of the XbaI polymorphism as compared to carriers of AG and GG genotypes (23.4% vs. 10.5%, p=0.02). TT and TC genotypes of the PvuII polymorphism were also associated with greater restenosis rate, as compared with genotype CC (19.3% vs. 3.1%, p=0.02). Associations for both polymorphisms were more expressed in women and in CEA patients. At multivariate analysis, T-A haplotype was a predictor of restenosis in the whole patient cohort (adjusted odds ratio, 7.85; 95% CI, 1.01–60.98). ConclusionPresence of A and T alleles (of the XbaI and PvuII polymorphisms, respectively) were associated with higher incidence of carotid restenosis, while the presence of G and C alleles (of the XbaI and PvuII polymorphisms, respectively) were associated with lower incidence of carotid restenosis.

Association of estrogen receptor α gene polymorphism with the presence of coronary artery disease documented by coronary angiography

Objectives To examine the relationship between PvuII and XbaI polymorphisms, with the presence of angiographically determined CAD in an Iranian population. Design and methods Patients having angiographic evidence of atherosclerosis (Gensini score > 6) in their epicardial coronary tree (CAD + case group) were compared with Patients with Gensini score ≤ 6 (CAD − control group). The presence of PvuII and XbaI polymorphisms was analyzed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Results The PvuIΙ genotype distributions were not statistically different in CAD groups, and subgroups stratified by gender. For the XbaI polymorphism, after controlling for age, male sex, cigarette smoking and hyperlipidemia, XbaI GG genotype was not also found to be an independent predictor for CAD occurrence (OR = 1.65; 95% CI: 0.90–3.03; P = 0.10). Conclusions We did not observe an association between ESR1 PvuII and XbaI gene polymorphisms with CAD in the risk of CAD in an Iranian population.