Biomedical subjects

H Deng

Publications and source records attributed to H Deng.

At least 55 records · Page 3Linked to original sources

PubMed2001

Is population bone mineral density variation linked to the marker D11S987 on chromosome 11q12-13?

Our purpose is to test linkage of human chromosome 11q12-13 to BMD variation. Chromosome 11q12-13 has been linked to three BMD-related phenotypes that are inherited as Mendelian traits in human pedigrees: an autosomal dominant high bone mass trait, autosomal recessive osteoporosis pseudoglioma, and autosomal recessive osteopetrosis. A sibling pair study with 374 sibships showed significant linkage of D11S987 to normal BMD variation, with a maximum logarithm of odds score of 3.5. However, a subsequent linkage study with a total of 595 sibling pairs demonstrated reduced significance for linkage of D11S987 to bone mineral density variation, with a logarithm of odds score less than 2.2. We genotyped five markers in a genomic region of approximately 27 cM centering on D11S987 and measured bone mineral density and other traits (weight, etc.) for 635 individuals from 53 human pedigrees. Each of these pedigrees was ascertained through a proband with bone mineral density Z-scores less than -1.28 at the hip or spine. Adjusting for age, sex, and weight as covariates, we performed two-point and multipoint linkage analyses using the variance component linkage analysis method implemented in Sequential Oligogenic Linkage Analysis Routines. We found little evidence of linkage of these five markers to bone mineral density at the spine, hip, wrist and total body bone mineral content. The maximum logarithm of odds score at these five markers was 0.25, and the maximum logarithm of odds score at D11S987 was 0.15. Therefore, although we cannot exclude the linkage of D11S987 region to bone mineral density variation, there is no evidence for linkage of the marker D11S987 on human chromosome 11q12-13 to bone mineral density variation in our study population.

Adult↗

PubMed2001

[Serum markers and pathological evaluation in hepatitis fibrosis of chronic hepatitis B treated with interferon alpha].

OBJECTIVE: To evaluate the anti-fibrotic effect of interferon alpha and to study the relationship between the anti-fibrotic effect and the efficacy of anti-virus in patients with chronic hepatitis B treated with interferon alpha. METHODS: Thirty-six patients with chronic hepatitis B were treated with interferon alpha. Before, during and after the treatment, the levels of hyaluronic acid (HA), type III procollagen (PC-III), type IV collagen(IV-C), laminin (LN) and transforming growth factor beta 1 (TGF-beta 1) were measured as the markers of hepatic fibrosis. Needle biopsy sections of the liver taken before and at the end of IFN treatment were assessed and compared according to the modified histological activity index (HAI) and hepatic fibrosis (HF) scoring system. RESULTS: In IFN group, the levels of HA, PC-III, IV-C, LN, and TGF-beta 1 after treatment were all significantly lower than those before treatment (P<0.01). The levels of HA, PC-III, and TGF-beta 1 after treatment were significantly lower in IFN group than in control one. HAI scores decreased from 9.3+/-3.2 to 6.2 +/-2.1 and HF scores decreased from 7.5+/-2.2 to 5.1+/-1.8 after treatment. CONCLUSIONS: The improvement of hepatic fibrosis closely related to the efficacy of anti-virus. Interferon alpha therapy is effective for hepatic fibrosis of chronic hepatitis B.

Adolescent↗

PubMed2001

[Linkage disequilibrium analysis of chromosome 22 and schizophrenia in a Chinese population].

OBJECTIVE: To explore the molecular genetic relations of chromosome 22 and schizophrenia and locate the susceptibility gene of schizophrenia. METHODS: Six dinucleotide tandem repeat loci on chromosome 22 were chosen to analyze 126 affected sib-pair nuclear families of schizophrenia in Chinese population by fluorescent labeled auto-mated genotyping and transmission/ disequilibrium test(TDT). RESULTS: The TDT-chi square value of IL2Rbeta was 25.30(P=0.01), which suggests there is linkage disequilibrium between IL2R beta and schizophrenia. The P vaules of the other five loci (D22S944, D22S264, D22S303, D22S278 and CYP2D6) were greater than 0.05. CONCLUSION: A susceptive gene of schizophrenia may be located in IL2Rbeta locus or adjacent region.

Chromosomes, Human, Pair 22↗

PubMed2001

[Clinical study of P-gp, and bcl-2 protein expression in non-Hodgkin's lymphomas patients].

OBJECTIVE: To investigate the relationship between the expression of P-gp, P26-bcl-2 and the prognosis in intermediate and high grade non-Hodgkin's lymphomas (NHL). METHODS: Sixty cases of intermediate and high grade NHL were retrospectively reviewed using immunohistochemical method. All patients were received CHOP chemotherapy over 4 courses. RESULTS: P-gp was identified in 15 and P26-bcl-2 in 25 cases. The 3-year survival rates for patients with P26-bcl-2 (+) and P26-bcl-2 (-) were 37.64% and 76.80%, respectively (P < 0.005), and for patients with both positive P-gp and P26-bcl-2 and both negative were 15.38% and 48.48%, respectively (P = 0.038). CONCLUSIONS: There is direct relationship between the P-gp, P26-bcl-2 protein expression and the prognosis in intermediate and high grade non-Hodgkin's lymphoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

[The measurement of 153Sm-EDTMP bone uptake rate and its relationship with therapeutic effect].

OBJECTIVE: To evaluate the measurement of 153Sm-EDTMP Bone uptake rate with whole-body scintigraphy and analyze the relationship between bone uptake rate and therapeutic effect. METHODS: 66 patients with bony metastases were examined with whole-body scintigraphy 10 minutes and 6 hours after the administration of 153Sm-EDTMP, and then bone uptake rate was calculated. RESULTS: The bone uptake rate in 66 patients ranged from 31.9% to 86.6%, (mean 56.0%). The patients with higher bone uptake rate had better overall therapeutic effect. According to the bone uptake rate calculated by whole-body scintigraphy, the therapy activity administered within the limit of bone marrow absorbed dose of 1400 mGy in these patients was 1.40-2.27GBq (mean 1.90 GBq). CONCLUSION: The present authors have developed a whole-body scintigraphic technique which is simple and reliable in calculating prospectively a safe and effective dose of 153Sm-EDTMP for palliating the patient's painful bone metastases without myelotoxicity.

Adult↗

PubMed2000

Regulation of ROMK1 channels by protein-tyrosine kinase and -tyrosine phosphatase.

We have used the two-electrode voltage clamp technique and the patch clamp technique to investigate the regulation of ROMK1 channels by protein-tyrosine phosphatase (PTP) and protein-tyrosine kinase (PTK) in oocytes coexpressing ROMK1 and cSrc. Western blot analysis detected the presence of the endogenous PTP-1D isoform in the oocytes. Addition of phenylarsine oxide (PAO), an inhibitor of PTP, reversibly reduced K(+) current by 55% in oocytes coinjected with ROMK1 and cSrc. In contrast, PAO had no significant effect on K(+) current in oocytes injected with ROMK1 alone. Moreover, application of herbimycin A, an inhibitor of PTK, increased K(+) current by 120% and completely abolished the effect of PAO in oocytes coexpressing ROMK1 and cSrc. The effects of herbimycin A and PAO were absent in oocytes expressing the ROMK1 mutant R1Y337A in which the tyrosine residue at position 337 was mutated to alanine. However, addition of exogenous cSrc had no significant effect on the activity of ROMK1 channels in inside-out patches. Moreover, the effect of PAO was completely abolished by treatment of oocytes with 20% sucrose and 250 microg/ml concanavalin A, agents that inhibit the endocytosis of ROMK1 channels. Furthermore, the effect of herbimycin A is absent in the oocytes pretreated with either colchicine, an inhibitor of microtubules, or taxol, an agent that freezes microtubules. We conclude that PTP and PTK play an important role in regulating ROMK1 channels. Inhibiting PTP increases the internalization of ROMK1 channels, whereas blocking PTK stimulates the insertion of ROMK1 channels.

Alanine↗

PubMed2000

A vibrational structure of 7,8-dihydrobiopterin bound to dihydroneopterin aldolase.

Dihydroneopterin aldolase (DHNA) catalyzes the conversion of 7, 8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin and glycolaldehyde. An inhibitor of the enzyme, 7,8-dihydrobiopterin, free in solution and bound in its complex with the enzyme has been studied by Raman difference spectroscopy. By using isotopically labeled 7,8-dihydrobiopterin and normal mode analyses based on ab initio quantum mechanic methods, we have positively identified some of the Raman bands in the enzyme-bound inhibitor, particularly the important N5=C6 stretch mode. The spectrum of the enzyme-bound inhibitor shows that the pK(a) of N5 is not significantly increased in the complex. This result suggests that N5 of 7,8-dihydroneopterin is not protonated before the bond cleavage of 7,8-dihydroneopterin during the DHNA-catalyzed reaction as has been suggested. Our results also show that the N5=C6 stretch mode of 7, 8-dihydrobiopterin shifts 19 cm(-)(1) upon binding to DHNA. Various possibilities on how the enzyme can bring about such large frequency change of the N5=C6 stretch mode are discussed.

Aldehyde-Lyases↗

PubMed2000

Structural basis of polyamine-DNA recognition: spermidine and spermine interactions with genomic B-DNAs of different GC content probed by Raman spectroscopy.

Four genomic DNAs of differing GC content (Micrococcus luteus, 72% GC; Escherichia coli, 50% GC; calf thymus, 42% GC; Clostridium perfringens, 27% GC) have been employed as targets of interaction by the cationic polyamines spermidine ([H(3)N(CH(2))(3)NH(2)(CH(2))(4)NH(3)](3+)) and spermine ([(CH(2))(4)(NH(2)(CH(2))(3)NH(3))(2)](4+)). In solutions containing 60 mM DNA phosphate (approximately 20 mg DNA/ml) and either 1, 5 or 60 mM polyamine, only Raman bands associated with the phosphates exhibit large spectral changes, demonstrating that B-DNA phosphates are the primary targets of interaction. Phosphate perturbations, which are independent of base composition, are consistent with a model of non-specific cation binding in which delocalized polyamines diffuse along DNA while confined by the strong electrostatic potential gradient perpendicular to the helix axis. This finding provides experimental support for models in which polyamine-induced DNA condensation is driven by non-specific electrostatic binding. The Raman spectra also demonstrate that major groove sites (guanine N7 and thymine C5H(3)) are less affected than phosphates by polyamine-DNA interactions. Modest dependence of polyamine binding on genome base composition suggests that sequence context plays only a secondary role in recognition. Importantly, the results demonstrate that polyamine binding has a negligible effect on the native B-form secondary structure. The capability of spermidine or spermine to bind and condense genomic B-DNA without disrupting the native structure must be taken into account when considering DNA organization within bacterial nucleoids or cell nuclei.

Animals↗

PubMed2000

Nuclear factor kappaB subunits induce epithelial cell growth arrest.

Nuclear factor kappaB (NF-kappaB) gene-regulatory proteins play important roles in inflammation, neoplasia, and programmed cell death. Recently, blockade of NF-kappaB function has been shown to result in epithelial hyperplasia, suggesting a potential role for NF-kappaB in negative growth regulation. We expressed active NF-kappaB subunits in normal epithelial cells and found that NF-kappaB profoundly inhibits cell cycle progression. This growth inhibition is resistant to mitogenic stimuli and is accompanied by other features of irreversible growth arrest. NF-kappaB-triggered cell cycle arrest is also associated with selective induction of the cyclin-dependent kinase inhibitor p21CiP1, with overexpression of p21(Cip1) alone inducing findings similar to those seen with NF-kappaB in vitro. An active NF-kappaB subunit expressed in the epidermis of p21(CiP1-/- mice, however, displays only partial growth-inhibitory effects, suggesting that full NF-kappaB growth inhibition is only partially p21(Cip1) dependent in this setting. These data indicate that NF-kappaB can trigger cell cycle arrest in epithelial cells in association with selective induction of a cell cycle inhibitor.

Animals↗

PubMed2000

Topology of catalytic portion of prostaglandin I(2) synthase: identification by molecular modeling-guided site-specific antibodies.

Prostaglandin I(2) synthase (PGIS) is an eicosanoid-synthesizing cytochrome P450, located in the endoplasmic reticulum (ER) membrane. The membrane topology of the catalytic portion of PGIS is still unknown. General models of the membrane topology of microsomal P450s have been proposed in two forms: (a) large part of the polypeptide exposed on the cytoplasmic side with an NH(2)-terminal membrane anchor to the ER membrane and (b) deep immersion of the polypeptide in the membrane, as described by J. P. Miller et al. (1996, Biochemistry 35, 1466-1474). We have characterized the membrane topology of catalytic portion of PGIS using molecular modeling-guided site-specific antibodies. A 3D working model of PGIS was constructed by homology modeling using P450(BM-3) crystal structure as a template (S. K. Shyue et al., 1997, J. Biol. Chem. 272, 3657-3662). Three hydrophilic peptides corresponding to different regions of the surface portion of PGIS with residues 109-127 (P109-127), 353-368 (P353-368), and 411-431 (P411-431) predicted from the model and an NH(2)-terminal hydrophobic peptide (residues 1-28, P1-28) were synthesized and used to prepare site-specific antibodies. All three of the hydrophilic peptide antibodies have high titer and are specifically recognized human PGIS, as shown by binding assays and Western blot analysis. In contrast, the hydrophobic NH(2)-terminal peptide has a much lower titer binding to the PGIS protein. The overall arrangement of the PGIS polypeptide with respect to the endoplasmic reticulum (ER) membrane was examined by immunocytochemistry techniques in transiently transfected COS-1 cells with recombinant human PGIS cDNA and in ECV cells expressing endogenous PGIS. The immunofluorescence staining for the cells with selective permeabilization of the plasma membrane using streptolysin O indicated that all three of the hydrophilic peptide antibodies bound to the cytoplasmic surface of the ER membrane. These results provide direct experimental evidence supporting the predicted 3D protein topological model in which the segments are located on the protein surface and the membrane topological model in which PGIS is largely exposed on the cytoplasmic side of the ER membrane. It also led us to conclude that the PGIS substrate, prostaglandin H(2) (PGH(2)), produced by prostaglandin H(2) synthase (PGHS) in the ER lumenal side must pass through the ER membrane barrier to the catalytic site of the PGIS in the cytoplasmic side of the ER membrane.

Amino Acid Sequence↗

PubMed2000

Cutting edge: introduction of an endopeptidase cleavage motif into a determinant flanking region of hen egg lysozyme results in enhanced T cell determinant display.

The choice of which determinants of a whole Ag will be presented on cell surface MHC class II molecules after uptake and processing by APC is the result of the interplay between structural characteristics of the Ag and the processing machinery of the APC. In this study, we demonstrate that introduction of a dibasic motif adjacent to a subdominant determinant enhances the presentation of this determinant from the whole molecule. This is the first report showing that a single amino acid substitution in a whole Ag, designed to introduce an endopeptidase recognition site, enhances display of class II-restricted determinants, most likely by creating a peptide chain cleavage in the antigenic molecule. Our findings have important implications for the understanding of immunodominance and for vaccine design.

Amino Acid Motifs↗

PubMed2000

Electrochemically modulated liquid chromatography coupled on-line with electrospray mass spectrometry.

Electrochemically modulated liquid chromatography (EMLC) has been coupled to an electrospray mass spectrometer. This combination takes advantage of the ability of EMLC to manipulate retention and enhance separation efficiency solely through changes in the potential applied to a conductive stationary phase, thereby minimizing complications because of possible changes in analyte ionization efficiencies when gradient elution techniques are used. Three examples are presented that demonstrate the attributes of this EMLC/electrospray mass spectrometry (ES-MS) coupling. The first two examples involve the separation of mixtures of corticosteroids or of benzodiazepines, showing the general utility of the union for eluent identification and low-level detection. The ability to identify products from on-column redox transformations is also demonstrated using the benzodiazepine mixture. The third example investigates the electrooxidation of aniline by utilizing an EMLC column as an on-line electrochemical reactor and product separator and ES-MS for detection and product identification.

Adrenal Cortex Hormones↗

PubMed2000

Electrochemically modulated preconcentration and matrix elimination for organic analytes coupled on-line with electrospray mass spectrometry.

Demonstrated for the first time is the use of electrochemically modulated preconcentration and sample matrix elimination combined on-line with electrospray mass spectrometry (EMPM/ES-MS) for the enhanced analysis of organics by ES-MS. EMPM is similar to adsorptive stripping analysis. Accumulation of the targeted analytes at the working electrode of an on-line electrochemical flow cell is accomplished via a nonelectrolytic adsorption process that is controlled through the proper combination of the solvent system, the working electrode material, and applied potential. Once on the electrode, the analyte may be washed free of sample matrix components detrimental to mass spectrometric detection. The potential applied to the electrode during the detection step is chosen to release or strip the analytes unaltered back into the solvent stream for mass spectrometric detection rather than to oxidize or reduce them as would be the case for electrochemical detection. Thus, retention and elution of a target analyte with EMPM are controlled by switching the working electrode potential, rather than via a switch in mobile-phase composition, as is done in more traditional preconcentration and cleanup schemes used on-line with ES-MS. The proof-of-principle studies described here use the breast cancer drug tamoxifen and a metabolite, 4-hydroxytamoxifen, as the target analytes. A thin-layer, flow-by electrode cell with a glassy carbon working electrode is used as the preconcentration device. The nature of the working electrode, the solvent systems, and the electrode potentials necessary to accumulate and strip tamoxifen and 4-hydroxytamoxifen are discussed. Calibration curves were fitted using the Langmuir isotherm. Detection limits (DLs) using a 5.0 min preconcentration period with selected reaction monitoring for tamoxifen (m/z 372 --> 72) were bracketed as 0.010 nM < DL < 0.025 nM. The ability to simultaneously detect low nanomolar levels of both tamoxifen and 4-hydroxytamoxifen in pristine solution and 1/10 diluted urine is also demonstrated.

Electrochemistry↗

PubMed2000

Processing and reactivity of T cell epitopes containing two cysteine residues from hen egg-white lysozyme (HEL74-90).

The Ag processing and structural requirements involved in the generation of a major T cell epitope from the hen egg-white lysozyme protein (HEL74-88), containing two cysteine residues at positions 76 and 80, were investigated. Several T cell hybridomas derived from both low responder (I-Ab) and high responder (I-Ak) mice recognize this region. These hybridomas are strongly responsive to native HEL, but unresponsive to the reduced and carboxymethylated protein. Air-oxidized HEL74-88 peptide was unable to bind I-Ak molecules and failed to stimulate T cells in the absence of intracellular Ag processing. Further functional competition assays showed that alkylation of cysteine residues with bulky methyl groups interferes with the contacts for the MHC class II molecules (I-Ak) of high responder mice and the I-Ab-restricted TCR of low responder mice. Serine substitutions of the cysteine residues of HEL74-88 either enhanced or abrogated T cell stimulation by the peptides without significant alterations in the class II binding. These results suggest that the cysteine residues of peptides must be free from disulfide bonding for efficient stimulation of T cells and yet frequently used modifications of cysteine residues may not be suitable for peptide-based vaccine development.

Amino Acid Sequence↗

PubMed2000

Determination of bone mineral density of the hip and spine in human pedigrees by genetic and life-style factors.

In 40 human pedigrees with 563 subjects, we evaluated the contribution of genetic and life-style factors (exercise, smoking, and alcohol consumption) and the interactions between non-genetic factors in determining bone mineral density (BMD) of the hip and spine. In our analysis, we adjusted for age, weight, height, menopausal status in females, life-style factors, and the significant interactions among these factors. For the spine and hip BMD, heritabilities (h(2)) (+/- SE) were, respectively, 0.68 (0.21) and 0.86 (0.28) in males and 0.64 (0.13) and 0.67 (0.14) in females. Exercise had significant beneficial effects for male spine BMD and female hip BMD. Alcohol consumption experienced in our sample had significant beneficial effects on hip BMD in both sexes. Although the main effect of smoking was not significant, there were significant interaction effects between smoking and other important factors (e.g., exercise, weight, alcohol consumption). For example, for female spine BMD, exercise had significant beneficial effects in smokers; however, its effect in non-smokers was non-significant. This result indicates that exercise may reduce deleterious effects of smoking (if any) on BMD, but may have minor effects in increasing BMD in non-smokers. The various interaction effects among risk factors explicitly revealed here for the first time indicate that the detailed effects and direction of individual risk factors may depend on the presence and magnitude of other factors. Weight invariably affected BMD of the hip and spine in both sexes. Age effects were significant for hip BMD, but not for male spine BMD.

Alcohol Drinking↗

PubMed2000

Identification of a locus for disseminated superficial actinic porokeratosis at chromosome 12q23.2-24.1.

Disseminated superficial actinic porokeratosis is an autosomal dominant cutaneous disorder characterized by many uniformly small, minimal, annular, anhidrotic, and keratotic lesions. The genetic basis for this disease is unknown. Using a genomewide search in a large Chinese family, we identified a locus at chromosome 12q23.2-24. 1 responsible for disseminated superficial actinic porokeratosis. The fine mapping study indicates that the disseminated superficial actinic porokeratosis gene is located within a 9.6 cM region between markers D12S1727 and D12S1605, with a maximum two-point LOD score of 20.53 (theta = 0.00) at D12S78. This is the first locus identified for a genetic disease where the major phenotype is porokeratosis. The study provides a map location for isolation of a gene causing disseminated superficial actinic porokeratosis.

China↗

PubMed2000

Lung inflammation in hyperoxia can be prevented by antichemokine treatment in newborn rats.

Hyperoxia may contribute to lung disease in newborns through effects on alveolar neutrophils which predominate in respiratory distress syndrome and other acute lung injuries. Neutrophil chemokines such as interleukin-8 (IL-8) regulate chemoattraction, and are elevated in tracheal aspirates of newborns who develop bronchopulmonary dysplasia (BPD). Blockade of neutrophil chemokines may reduce hyperoxia-induced inflammatory lung injury and BPD. We therefore tested the hypothesis that hyperoxia contributes to elevations of rat neutrophil chemokines, cytokine-induced neutrophil chemoattractant-1 (CINC-1), and macrophage inflammatory protein-2 (MIP-2) in newborn rat lung. Newborn rats were exposed to air or 95% O(2) for 8 d. CINC-1 and MIP-2 were measured in whole lung homogenates by ELISA. Newborn 95% O(2)-exposed animals were given anti-CINC-1 or anti-MIP-2, 1, 5, or 10 microg on Days 3 and 4 of 95% O(2) exposure. Bronchoalveolar lavage (BAL) was performed after perfusion on day 6 to evaluate airway neutrophils, and myeloperoxidase (MPO) was measured in perfused whole lung. Lungs were examined histologically and immunohistochemically for effects of 95% O(2) +/- antichemokine. CINC-1 and MIP-2 increased nearly tenfold by Day 8 95% O(2) treatment versus air control. CINC-1 and MIP-2 immunolabeling was increased in alveolar macrophages and alveolar epithelium in 95% O(2). Anti-CINC-1 and anti-MIP-2 treatment at every dose reduced neutrophil number > 90% in BAL. Anti-CINC-1 10 microg reduced tissue MPO by 50%. Antichemokine treatment on days 3 and 4 prevented alveolar septal thickening and reduced chemokine immunolabeling on Day 6. Hyperoxia-induced neutrophil influx is mediated in part by CINC-1 and MIP-2 in newborn rats and can be partially prevented by treatment with anti-CINC-1 and anti-MIP-2.

Acute Disease↗

PubMed2000

Association of estrogen receptor-alpha genotypes with body mass index in normal healthy postmenopausal Caucasian women.

Several lines of evidence suggest the importance of the estrogen receptor (ER) in determining body mass index (BMI). Our purpose was to investigate whether genetic polymorphisms at the restriction enzyme PvuII site of the ER-alpha gene locus are associated with BMI variation. Data on BMI, age, and ER-alpha genotypes were obtained from 108 healthy midwestern U.S. postmenopausal Caucasian women. The study subjects were unrelated and aged 65 yr and over (mean age +/- SD, 73.4 +/- 5.1 yr), with an average BMI of 25.25 (SD, 4.04). The ER-alpha genotypes were obtained by PCR followed by restriction enzyme PvuII digestion. We found that in our study subjects the ER-alpha genotypes are significantly associated with BMI (by ANOVA, P = 0.04), explaining about 6.2% of the BMI variation in our study sample. The allelic effects of this locus on BMI are approximately additive. In our sample, individuals of the PP and Pp genotypes have, respectively, 11.4% and 4.8% higher BMI than individuals of the pp genotype. There is a significant ER-alpha genotype by age interaction, so that in our sample PP individuals tend to gain weight with age, whereas Pp and pp individuals tend to lose weight with age. Therefore, the ER-alpha polymorphisms are associated with BMI variation in healthy postmenopausal Caucasian women aged 65 yr and over. Our result is consistent with some recent findings suggesting the potential effects of the ER on BMI. The importance of the ER-alpha genotypes in other populations and other age groups needs to be demonstrated. Although the results of the ER-alpha genotype by age interaction are obtained here from cross-sectional data, direct confirmation may come from longitudinal studies in which individuals are measured multiple times over several years. The importance of the ER-alpha genotypes on BMI should be confirmed by further studies using methods robust to the potential problem of population substructuring that may confound the conclusions of population association studies.

Aged↗