Systematic Mutation Screening of the Estrogen Receptor Beta Gene in Probands of Different Weight Extremes: Identification of Several Genetic Variants

Rosenkranz, K.; Hinney, Anke; Ziegler, Andreas; Hermann, H; Fichter, M.; Mayer, Herbert; Siegfried, Wolfgang; Jk, Young; Remschmidt, Helmut; Hebebrand, Johannes

doi:10.1210/jcem.83.12.5471

Cited by 104 publications

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“…10 Two single nucleotide polymorphisms (SNPs) in this gene were described by Rosenkranz et al, 11 a RsaI restriction site at 1082G4A (a silent mutation in exon 5) and an AluI restriction site at 1730A4G (3' nontranslated region of the exon 8). The progesterone receptor gene is located on chromosome 11q22-23, 12 and Rowe et al 13 identified a 306-bp insertion of the PV/HS-1 Alu subfamily in intron 7, denominated PROGINS.…”

Section: Introductionmentioning

confidence: 99%

Estrogen receptor 2 and progesterone receptor gene polymorphisms and lipid levels in women with different hormonal status

et al. 2004

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Sex steroid hormones have multiple effects on lipid metabolism. We investigated the association between two common single nucleotide polymorphisms of the estrogen receptor 2 gene (ESR2), 1082G4A and 1730A4G, and PROGINS polymorphism of the progesterone receptor gene (PGR) with lipoprotein levels in a cross-sectional study with 472 women of European descent. The women were classified into three subgroups according to hormonal status, premenopausal women (n ¼ 187; mean age ¼ 3479.7 years), postmenopausal women exposed to hormone replacement therapy (HRT) (n ¼ 118; 5676.7 years) and postmenopausal women unexposed to HRT (n ¼ 167; 5879.8 years). The premenopausal and postmenopausal women exposed to HRT, both carriers of G/A genotype, exhibited LDL-C (P ¼ 0.027 and 0.001, respectively) and T-chol levels (P ¼ 0.035 and 0.001, respectively) lower than carriers of G/G genotype. This association was not observed in postmenopausal women unexposed to HRT. These results suggest that ESR2 1082G4A genotype may influence LDL-C levels in women with abundant estrogen levels, due to either endogenous or exogenous sources. INTRODUCTIONEndogenous and exogenous sex steroid hormones have multiple effects on lipid and lipoprotein metabolism. The oral estrogen replacement therapy (ERT) in postmenopausal women decreases serum total cholesterol (T-chol) and lowdensity lipoprotein cholesterol (LDL-C) concentrations, as well as increases serum high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels. 1 The effects of combined (estrogen plus progestin) hormone replacement therapy (HRT) are uncertain; the addition of a progestogen to estrogens tends to attenuate the increase in serum HDL-C and the decrease in LDL-C, obtained with ERT, although this effect seems to be related to the dose and to androgenic potency of the progestogen. 2 The beneficial changes in these lipoproteins should be associated with at least 30-35% decline in coronary heart disease (CHD) incidence. 3 However, the results from the Heart and Estrogen/Progestin Replacement Study (HERS) 4 and the Women's Health Initiative (WHI) trial 5 demonstrated that oral HRT does not provide cardiovascular benefit or even some evidence of cardiovascular harm.

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Section: Introductionmentioning

confidence: 99%

Estrogen receptor 2 and progesterone receptor gene polymorphisms and lipid levels in women with different hormonal status

et al. 2004

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“…At the ESR2 locus the genotype of each individual was determined at a dinucleotide repeat 17 and two previously described SNPs (G1082A and A1730G) located in exon 5 and 8 respectively. 9 The distribution of the alleles at the dinucleoide repeat ESR1 in the control and AN populations is shown in Figure 1. Statistical analysis using the 'Clump' 19 computer package fails to show any signifi- cant difference in the distribution of alleles between the AN and control population ( 2 = 8.04, P Ͼ 0.2, df = 18).…”

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“…However the two SNPs studied at the ESR2 locus have previously been investigated in an AN population. 9 This study does not replicate the findings of Rosenkrantz et al 19 for suggestive evidence for association of the 1082G allele (nominal P value = 0.04) with AN, 8 conversely this study reports an association with the heterozygous genotype G1082A. The present study observed an increased frequency of the 1082A allele in the AN population ( 2 = 11.46, P = 0.0007, df = 1) which results in the genotype frequencies in this population alone deviating from Hardy-Weinberg equilibrium.…”

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“…Also given the low frequency of the 1082A allele and the discrepancies between the two studies, replication in a larger cohort is necessary in order to verify these findings. Rosenkrantz's study 9 was based on a German population whereas this study sampled British white Caucasians therefore the differences may arise from genetic heterogeneity between these populations.…”

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Variation in the ESR1 and ESR2 genes and genetic susceptibility to anorexia nervosa

et al. 2002

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There is significant evidence for genetic factors in the susceptibility to anorexia nervosa (AN). Previously genetic variation in the estrogen receptor 2 gene (ESR2) has been studied, however no strong evidence of association with AN has been found. In the present study variation in the estrogen receptor 1 (ESR1) and ESR2 genes was examined. Estrogen receptors have been localised to areas of the brain involved in behaviour and regulation of food intake. The anorexic effects of estrogen are accentuated by stress and thus it is postulated that variation in the estrogen receptors may contribute to the genetic susceptibility to AN in females. A cohort of 170 female, Caucasian AN sufferers and 152 female controls were typed for dinucleotide repeat polymorphisms in both ESR1 and ESR2 and two further SNPs at each locus. Variation at ESR1 was not associated with AN. However an association was found at the ESR2 locus with the heterozygous genotype of the G1082A polymorphism and AN but not with any of the other ESR2 polymorphisms analysed. Analysis of haplotypes at ESR1 and ESR2 showed no significant evidence of association with AN suggesting that the variability in ESR2 alone may contribute to the genetic susceptibility to AN. Molecular Psychiatry (2002) 7, 86-89. DOI: 10.1038/ sj/mp/4000929More than 90% of AN sufferers are female. It is generally accepted that the age of onset of AN shows a bimodal distribution 1 with one peak at or around the age of puberty in females when estrogen levels are dramatically increased. Estrogen receptors in the brain colocalise with corticotrophin releasing factor (CRF) 2 suggesting an interaction between estrogen and CRF may modulate the hypothalamic pituitary adrenal (HPA) axis. The disruption of the HPA axis in AN sufferers cannot be wholly attributed to the effects of semi-starvation 3 and the HPA axis is also elevated in response to stress. 4,5 In rodents and primates high estrogen levels are known to have an inhibitory effect on food intake. 6 This led us to postulate that estrogen may be involved in the genetic disposition to AN. Estrogen interacts in both the periphery and the central nervous system via at least two different estrogen receptors (ESR1 and ESR2). 7,8 Previously Rosenkranz et al reported genetic variations in the ESR2 (ESR-beta) gene in probands of different weight extremes (including patients with AN and bulimia nervosa) and reported suggestive evidence of an association with susceptibility to AN. 9 ESR1 has been shown to play a role in behaviour in mice 10 and more recently variants of the ESR1 gene have been implicated in anxiety. 11 As it has previously been suggested that anxiety may accentuate the anorexic effects of estrogen, 12 we postulate that the interaction of stress and estrogen may modulate the HPA axis in the pathogenesis of anorexia nervosa. Both ESR1 and 2 are localised to the amygdaloid complex, 13 an area known to be critical in the control of emotions. These receptors are known to form heterodimers in vitro 14 and therefore this study aimed to inv...

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“…The anorectic effects of estrogens have been noted for decades 46,47 and the estrogen receptor b (ERb) gene has shown associations with both AN and BN. 48,49 This gene is also located on chromosome 14, which was found to be in significant linkage with BN. 43 Interestingly, serotonin receptors are regulated by estrogen with estrogen affecting serotonin gene transcription.…”

Section: Int J Eat Disord 37 S43-s48 2005mentioning

confidence: 99%

A review and primer of molecular genetic studies of anorexia nervosa

Klump

Gobrogge²

2005

Int. J. Eat. Disord.

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Systematic Mutation Screening of the Estrogen Receptor Beta Gene in Probands of Different Weight Extremes: Identification of Several Genetic Variants

Cited by 104 publications

References 0 publications

Estrogen receptor 2 and progesterone receptor gene polymorphisms and lipid levels in women with different hormonal status

Estrogen receptor 2 and progesterone receptor gene polymorphisms and lipid levels in women with different hormonal status

Variation in the ESR1 and ESR2 genes and genetic susceptibility to anorexia nervosa

A review and primer of molecular genetic studies of anorexia nervosa

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