Receptor-α Gene Polymorphism Research Articles

Genetic polymorphism of liver X receptor gene in vitiligo: Does it have an association?

Vitiligo is an acquired depigmentation of the skin and the mucous membranes, exhibited as white macules and patches due to selective loss of melanocytes. Etiological theories of vitiligo include genetic, immunological, neurohormonal, cytotoxic, biochemical, oxidative stress, and newer theories of melanocytorrhagy and diminished melanocytes survival. It has been revealed that liver X receptor alpha gene is expressed in skin tissue such as sebaceous glands, hair follicle, keratinocytes, and fibroblasts and is linked to various skin disorders as acne vulgaris and psoriasis. To evaluate the association between liver X receptor-α gene polymorphism (rs11039155 and rs2279238) and vitiligo and whether they are related to disease activity and severity or not. 50 vitiligo patients and 20 age- and sex-matched apparently healthy controls were enrolled. All the included subjects were genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis technique for (-6G/A) and (+1257C/T) SNPs. Significant statistical difference between cases and controls regarding genotype and allele frequencies for -6G/A polymorphism with predominance of AA genotype (OR: 5.1, 95% CI: 1.6-15.9) and A allele (OR: 5.3, 95% CI: 1.6-15.9) in cases and also for +1257C/T polymorphism with predominance of TT genotype OR: 9.2 (95% CI: 1.4-82.9) and T allele OR: 3.4 (95% CI: 1.4-8.1) in vitiligo cases. No significant relationship between -6G/A genotypes nor +1257C/T genotypes and disease activity and severity. The study showed significant association between Liver X receptor gene polymorphisms (-6G/A, +1257 C/T) and development of vitiligo in Egyptian patients. However, it failed to show any relation with disease activity nor severity.

Interaction analysis between epidermal growth factor and peroxidase proliferators activate receptor-α gene polymorphism and susceptibility to generalized aggressive periodontitis

Objective: To explore the correlation and interaction between epidermal growth factor (EGF) rs2237051 and peroxidase proliferators activate receptor-α (PPAR-α) rs4253623 polymorphisms and the susceptibility of generalized aggressive periodontitis (GAgP). Methods: Two hundred and nineteen Chinese patients with GAgP were enrolled from the patients of the Department of Periodontology, Peking University School and Hospital of Stomatology from January 2001 to December 2015. The control group comprised 138 periodontally healthy volunteers recruited from the staff and students of the Peking University School and Hospital of Stomatology. The EGF rs2237051 and PPAR-α rs4253623 polymorphisms were genotyped using time-of-flight mass spectrometry. Logistic regression models were conducted to analyze the correlation between the EGF rs2237051 and PPAR-α rs4253623 variants with GAgP. The likelihood ratio test was used to analyze whether there was an interaction between the two polymorphisms in the susceptibility of GAgP. The interaction model adopted was the multiplication model. Results: The mean ages of GAgP group (male:87; female:132) and control group (male: 53; female: 85) were (27.3±4.5) years and (27.1±4.2) years respectively and there was no significant difference in age and gender distribution between the two groups. For EGF rs2237051, the frequency of AA genotype in the GAgP group [49.5% (107/216)] was significantly higher than that in the control group [37.7% (52/138)], and the frequency of AG/GG genotype in the GAgP group [50.5% (109/216)] was significantly lower than that in the control group [62.3% (86/138)](P<0.05). Compared with AA genotype, individuals with AG/GG genotype had a 39% lower risk of GAgP after adjustment of age and gender (OR: 0.61, 95%CI: 0.40-0.95, P<0.05). For PPAR-α rs4253623, the frequency of AA genotype in the GAgP group [76.2% (160/210)] was significantly higher than that in the control group [65.9%(81/123)], and the frequency of AG/GG genotype in the GAgP group [23.8% (50/210)] was significantly lower than that in the control group [34.1%(42/123)] (P<0.05). Compared with AA genotype, individuals with AG/GG genotype had a 40% lower risk of GAgP after adjustment of age and gender (OR: 0.60, 95%CI: 0.36-0.98, P<0.05). EGF rs2237051 and PPAR-α rs4253623 showed a significant interaction in the susceptibility to GAgP. Compared with AA genotype, the risk of GAgP in individuals with both AG/GG genotypes of EGF rs2237051 and PPAR-α rs4253623 was reduced by 66% (OR: 0.34, 95%CI: 0.17-0.66, P<0.01). Conclusions: EGF rs2237051 and PPAR-α rs4253623 are correlated with GAgP susceptibility, and there is a significant interaction between them in the susceptibility of GAgP. The G allele of the two loci has a protective effect on the disease of GAgP.

Correlation between estrogen receptor-α gene polymorphism and rheumatoid arthritis in females.

Correlation between estrogen receptor-α gene polymorphism and rheumatoid arthritis in females.

Effect of estrogen receptor-α gene polymorphism on serum osteoprotegerin and calcaneus bone density in postmenopausal women in Guangxi Zhuang nationality

Objective To investigate the effect of estrogen receptor-α gene polymorphism on osteoprotegerin(OPG)and calcaneus bone density in early and late postmenopausal women in Guangxi Zhuang nationality, in order to provide the theoretical basis for the early prevention and treatment of postmenopausal osteoporosis caused by estrogen receptor gene-induced osteoprotegerin reduction. Methods The broadband ultrasound attenuation in the right heel bone was measured by quantitative ultrasound bone densitometry in 621 postmenopausal women of Guangxi Zhuang nationality.Peripheral blood mononuclear cells and their DNA were extracted.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)was used to detect the estrogen receptor-α gene polymorphism.Serum osteoprotegerin level was determined by enzyme-linked immunosorbent assay.The differences of data distribution of OPG and calcaneus bone density were compared between five items of 3 genotypes and 2 alleles at the same age group of 40-, 45-, 50-, 55-, 60-, 65-, 70-, 75-80 years. Results Women aged 60 years and over versus those aged 40-59 years showed that serum osteoprotegerin(OPG)and bone mineral density(BMD)were decreased(P 0.05). Women aged 60 years and over showed that ER-α Puv Ⅱ polymorphism of allele big P versus p, Pp, pp, PP in the same age groups had significantly decreased serum osteoprotegerin and bone mineral density.Women aged 65 years and over showed that ER-α XbaⅠpolymorphism of heterozygote Xx versus xx, XX, X, x in the same age groups had a significantly increased serum osteoprotegerin and bone mineral density(P<0.05). Conclusions Women with big P allele of ER-α PvuⅡpolymorphism have low serum osteoprotegerin level and a decreased bone mineral density, who are prone to postmenopausal osteoporosis.Thus, P allele of ER-α PvuⅡpolymorphism is a causative agent.More attention should be paid to early prevention and treatment.But, women with the Xx heterozygote of ER-α XbaⅠpolymorphism have high serum osteoprotegerin level and an increased bone mineral density, who are not easy to suffer from postmenopausal osteoporosis.Therefore, Xx heterozygote of ER-α XbaⅠpolymorphism is a protective agent.The prevention and treatment of postmenopausal osteoporosis should be individualized based on estrogen receptor-α gene polymorphism. Key words: Zhuang nationality; Receptors, estrogen; Polymorphism, single nucleotide; Osteoprotegerin

Association between estrogen receptor-α gene polymorphisms and dermatomyositis in Bulgarian patients

Association between estrogen receptor-α gene polymorphisms and dermatomyositis in Bulgarian patients

Preliminary genetic imaging study of the association between estrogen receptor-α gene polymorphisms and harsh human maternal parenting

A failure of neural changes initiated by the estrogen surge in late pregnancy to reverse the valence of infant stimuli from aversive to rewarding is associated with dysfunctional maternal behavior in nonhuman mammals. Estrogen receptor-α plays the crucial role in mediating these neural effects of estrogen priming. This preliminary study examines associations between estrogen receptor-α gene polymorphisms and human maternal behavior. Two polymorphisms were associated with human negative maternal parenting. Furthermore, hemodynamic responses in functional magnetic resonance imaging to child stimuli in neural regions associated with social cognition fully mediated the association between genetic variation and negative parenting. This suggests testable hypotheses regarding a biological pathway between genetic variants and dysfunctional human maternal parenting.

Estrogen receptor-α gene polymorphism and endometriosis in a population in north of Iran

Estrogen receptor-α gene polymorphism and endometriosis in a population in north of Iran

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.

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.

No Genetic Association between the Myeloperoxidase Gene –463 Polymorphism and Estrogen Receptor-α Gene Polymorphisms and Japanese Sporadic Alzheimer’s Disease

Myeloperoxidase (MPO) presence has been demonstrated in microglia associated with senile plaques and contributes to Alzheimer’s disease (AD) pathology through oxidation-induced damage. MPO activity is normally higher in women than in men. Additionally, a functional biallelic (G/A) polymorphism in the promoter region (–463) of the MPO gene has been associated with a gender-specific risk factor for AD, but reports of this association have been inconsistent. Furthermore, estrogen is known to enhance MPO activity in myeloid cells and increases the amount of MPO in plasma. Recently, estrogen replacement therapy has been reported to reduce the risk of developing AD and to help maintain cognitive function in patients with AD. In the current study, we analyzed the MPO –463 polymorphism and two estrogen receptor-α polymorphisms in 205 Japanese sporadic AD patients and 92 controls. The results suggest that there is no significant difference in the genotypic frequencies and allelic frequencies of the MPO –463 polymorphism and the estrogen receptor-α polymorphisms between the Japanese sporadic AD group and the control group.

Estrogen-metabolizing gene polymorphisms, but not estrogen receptor-alpha gene polymorphisms, are associated with the onset of menarche in healthy postmenopausal Japanese women.

Both onset and cessation of menstruation have strong genetic inclination. We aimed to identify genetic factors influencing the onset of menarche and natural menopause in a Japanese population by investigating the polymorphisms of estrogen receptor-alpha and estrogen-metabolizing enzyme genes. Three hundred seventeen postmenopausal Japanese women, aged 46 yr and over, were enrolled in this study under informed consent. Genomic DNA was extracted from peripheral leukocytes, and PCR-based restriction fragment length polymorphism assays were used to determine estrogen receptor-alpha: PvuII, XbaI, and estrogen-metabolizing enzymes; CYP17, estrogen biosynthesis (high activity, A2/A2, CYP1A1), hydroxylation (high inducibility, vt/vt, and COMT), inactivation (low activity, L/L) genotypes. There were no significant differences in ages at menarche and natural menopause or years of menstruation among each PvuII or XbaI genotype and seven combinations of PvuII and XbaI genotypes. We found that ages at menarche in women with A1/A2 (higher activity of CYP17; 13.6 +/- 1.2 yr) were significantly earlier than in those with A1/A1 (lower activity of CYP17; 14.1 +/- 1.3 yr). There were no significant differences in age at natural menopause and years of menstruation among each CYP17, CYP1A1, or COMT genotype. The small sample size of each combination of estrogen-metabolizing genotypes made it impractical to evaluate the effects of the interdependency of each genotype, including extreme genotype categories such as A2/A2L/Lvt/vt vs. A1/A1H/Hwt/wt genotypes, on ages at menarche and/or natural menopause. The results suggest that the estrogen-metabolizing CYP17 genotype influences age at menarche in healthy postmenopausal Japanese women.

Association of the Estrogen Receptor-α Gene Polymorphism with the Risk of Endometriosis in Korean Women

Association of the Estrogen Receptor-α Gene Polymorphism with the Risk of Endometriosis in Korean Women

Relation of estrogen receptor-α gene polymorphism and hormone replacement therapy to fall risk and muscle strength in early postmenopausal women

BACKGROUND. Several factors may increase fracture risk, among them reduced bone mineral density (BMD), increased bone resorption, microarchitectural deterioration of bone, increased fall risk, and decreased muscle strength. We have previously reported that PvuII polymorphism of the estrogen receptor-α (ER α) gene is associated with bone loss rate, fracture risk, and response to hormone replacement therapy (HRT) in early postmenopausal Finnish women.METHOD. We studied the influence of the ERα genotype on fall risk and muscle strength in a 5-year randomized HRT trial of 331 early postmenopausal women (subgroup of the population-based OSTPRE study, Kuopio, Finland). A 5-year postal inquiry in May 1994 included questions on falls during the previous 12 months. Grip strength was measured with dynamometer. The ERα gene polymorphism was analysed using PCR and PvuII restriction enzyme digestion. RESULTS. In all, 97 out of the 331 women reported falls. Half of those (56%) were slip falls, mostly during the winter season. In the HRT group, the ERα genotype was associated with fall risk (P = 0.002, logistic regression). The risk of falls (RR) was higher in women with the PP genotype than in those with the Pp (RR = 5.26, 95% CI 1.98-13.94, P = 0.001) or the pp (RR = 3.84, 95% CI 1.46-10.12, P = 0.007) genotype. When the falls were divided into slip (environment-related) and non-slip (endogenous) falls, the non-slip falls were associated with the genotype (P = 0.004), but the slip falls were not so clearly (P = 0.061). When all falls and non-slip falls were adjusted to the number of chronic health disorders and the variable time-since-menopause, the difference between the genotypes persisted (P = 0.003 and P = 0.010, respectively). In the non-HRT group, the ERα genotype was not associated with fall risk. The baseline or the 5-year grip strength values were not influenced by the ERα genotype. In conclusion, ER α polymorphism is associated with fall risk, especially with non-slip falls, in early postmenopausal Finnish women during the HRT. We have previously reported that, during HRT, women with the P allele have decreased fracture risk and that they may preferentially derive benefit from the positive effect of HRT on BMD. This suggests that the influence of ERα polymorphism may depend on the target tissue (bone versus the nervous system). CONCLUSIONS. In these early postmenopausal, non-osteoporotic and relatively healthy women, the increased fall risk associated with the PP genotype was not associated with increased fracture risk, possibly due to improved bone strength during the HRT although falls generally predispose to fractures.

Genotype distribution of estrogen receptor-α gene polymorphisms in italian women with surgical uterine leiomyomas

Objective: To explore a possible association between estrogen receptor-α (ER-α) gene polymorphisms and development of uterine leiomyomas. Design: Case–control study. Setting: University teaching hospital. Patient(s): 119 women with clinically and surgically diagnosed uterine leiomyomas. Intervention(s): Therapeutic hysterectomy. Main Outcome Measure(s): Frequency and distribution of ER-α gene polymorphisms. Result(s): No statistically significant differences between controls and patients in the allele frequency and genotype distribution were found when Pvu II and Xba I restriction polymorphism sites were analyzed separately. When the two ER-α gene polymorphisms were analyzed in combination, five major genotypes were recognized in controls or patients; the frequency differed slightly but not significantly between groups. Conclusion(s): The Pvu II and Xba I polymorphisms in the ER-α gene do not produce different risks of developing uterine leiomyomas.