Potential influence of interleukin-1 haplotype IL-1 beta-511*T-IL-1RN*1 in conferring low risk to middle third location of esophageal cancer: a case-control study

Interleukin (IL)-1 gene polymorphisms affect several inflammatory diseases, including cancer. Therefore, we studied genetic association of biallelic (-511C>T) polymorphism of IL-1β and 86-bp VNTR polymorphism of IL-1RN in 159 patients with esophageal cancer (EC) and 194 age- and gender-matched healthy controls. Genetic analysis for IL-1 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of IL-1β (-511C>T) and IL-1RN (variable number tandem repeat) genotypes, alleles, and haplotypes did not differ significantly between patients and controls. However, IL-1β -511TT genotype and T1+ haplotype combination illustrated low risk for disease at the middle third location of the tumor (odds ratio [OR] = 0.27; 95% confidence interval [CI] = 0.11–0.62; p = 0.002; OR = 0.462; 95% CI = 0.253–0.845, p = 0.01). In conclusion, subjects with IL-1β -511TT genotype or IL-1β*T-IL-1RN*1 (T1) haplotype had lower risk for middle third tumor location of EC in a northern Indian population.     

The association of TIM-3 gene polymorphism with atopic disease in Korean population

The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is identified to be expressed on T cells. A member of the TIM family, TIM-3 is selectively expressed on the surface of differentiated T helper 1 (Th1) cells. TIM-3 might have an important role in the induction of autoimmune diseases by regulating macrophage activation and interacts with the TIM-3 ligand to regulate Th1 responses. In the present study, we analyzed the association of the genotype and allele frequencies between asthma or allergic rhinitis patients and nonatopic controls using large samples size at −1516G > T, −574T > G, and 4259G > T polymorphic sites of the Tim-3 gene. The genotype and allele frequencies of −574T > G polymorphism in asthma patients (p = 0.042 and p = 0.017, respectively) as well as allergic rhinitis patients (p = 0.008 and p = 0.003, respectively) were significantly different from those of nonatopic controls. Furthermore, the allele frequency of 4259G > T polymorphism in allergic rhinitis patients (p = 0.029) was also significantly different. Our results strongly suggest that the −574T > G polymorphism of Tim-3 might be associated with the susceptibility of atopic diseases such as asthma and allergic rhinitis.     

The association between mannose-binding lectin gene polymorphism and rheumatic heart disease

Mannan-binding lectin (MBL) is an innate pattern recognition molecule known to play a key role in pathogen clearance. As MBL2 gene polymorphism is associated to an increased susceptibility to infection, we aimed to determine genetic variations in the MBL2 gene in rheumatic heart disease (RHD). Genetic variations in the promoter and exon 1 region of the MBL2 gene were analyzed in 107 patients with RHD and 105 controls by real-time polymerase chain reaction. The frequency of MBL2* A/A genotype was significantly higher in RHD patients (71/107, 66.36% vs 52/105, 49.52%, p ≤ 0.02, OR = 1.99, 95% CI, 1.15–3.50). A/A genotypes were associated with higher levels of MBL in RHD compared with controls with the same genotype (p ≤ 0.004). The frequency of HYPA/HYPA, HYPA/LYQA, and LYQA/LYQA haplotypes was also increased in RHD (p ≤ 0.03, OR = 1.98, 95% CI, 1.05–3.73). However, the frequency of MBL2 variant alleles (termed “O”) was lower among patients (39/214, 18.2% vs 63/210, 30.0%, p ≤ 0.006, OR = 0.52, 95% CI, 0.33–0.82), which was also seen for O/O genotypes (3/107, 2.8% vs 10/105, 9.5%, p ≤ 0.05, OR = 0.27, 95% CI, 0.07–1.03). This data suggests a role for MBL genotypes in the susceptibility to RHD. However, it still remains unclear whether A/A homozygosity is a risk factor for RHD or rheumatic fever itself.     

Delayed Acquisition of Behavioral and Hippocampal Responses During Jaw Movement Conditioning in Aging Rabbits

Young (3–7 months; n = 7) and aging (40–49 months; n = 7) rabbits (Oryctolagus cuniculus) were classically conditioned in a trace jaw movement paradigm (300 ms tone, 450 ms trace, 200 ms intraoral water) after implantation of electrodes into area CA1 of dorsal hippocampus. Aging rabbits took significantly more trials to reach a behavioral criterion of 8 conditioned responses in any 9 consecutive trials than young rabbits (p = 0.04), and their conditioned, but not unconditioned, jaw movement responses were of a lower frequency than those of young rabbits (p = 0.02). Early in training, aging rabbits’ hippocampal responses were significantly smaller just before water onset than corresponding responses of young rabbits (p = .03). The magnitude of this response was negatively correlated with trials to criterion (r = −0.60, p = 0.03). These results are interpreted in terms of age-related differences in the hippocampal contribution to jaw movement learning.     

Association of MICA polymorphism with rheumatoid arthritis patients in Koreans

To investigate whether genetic variations of MICA are associated with susceptibility to rheumatoid arthritis (RA), the (GCT)n microsatellite polymorphism of the transmembrane domain was analyzed in 144 Korean patients with RA and in 297 unrelated healthy controls. The allele frequency of MICA*A9 significantly decreased in RA patients compared with controls (9.0% vs. 15.3%, odds ratio [OR] = 0.55, p = 0.0098, p_c = 0.049), whereas the frequency of the MICA*A4 and MICA*A5.1 alleles tended to increase in RA patients (21.2% vs. 14.8%, OR = 1.55, p = 0.018, p_c > 0.05; 20.5% vs. 15.0%, OR = 1.46, p = 0.0403, p_c > 0.05). By subgroup analysis, the MICA*A4 allele significantly increased in seropositive RA patients versus controls (23.0% vs. 14.8%, OR = 1.69, p = 0.0082, p_c = 0.041). HLA-DRB1*0405 was strongly associated with RA (p_c = 0.0000008), and strong linkage disequilibrium was observed between HLA-DRB1*0405 and MICA*A4 alleles in controls (p_c = 0.000004) as well as in RA patients (p_c = 0.0012). In Korean patients, HLA-DRB1*0405 was primarily associated with RA and the weak association of RA with MICA*A4 was secondary to that with HLA-DRB1*0405. Additionally, MICA*A9 might have a weak protective effect on the susceptibility to RA in Koreans.     

Association of IL-10 genotype with sudden infant death syndrome

Sudden infant death syndrome (SIDS) is a major cause of infant death of unknown etiology. We propose that SIDS results from a genetically determined imbalance in the production of inflammatory and anti-inflammatory cytokines in response to the infant’s microbial flora. We were especially interested to know the relationship between SIDS and genetically determined higher or lower production of IL-10, an anti-inflammatory cytokine. Biallelic polymorphisms in the promoter region of the IL-10 gene associated with higher or lower production of IL-10 were determined in a SIDS and in a control group using a sequence-specific oligonucleotide approach. One particular allele of the IL-10 gene, the IL-10-592*A allele, was significantly associated with SIDS. Indeed, 70% of the SIDS babies carried the IL-10-592*A allele (p = 0.007 compared with control). In addition, there was a significant reduction in the frequency of homozygosity for the allele IL-10-592*C (p = 0.001 compared with control). Carrying the A allele (either A/A or A/C) had an odds ratio of 3.3 (95% confidence interval 1.4–8.0). In the same patients there was no association with other IL-10 gene polymorphisms nor with other cytokine (TNF-, TGF-β1) genotypes, emphasizing the particular relationship between SIDS and the IL-10-592*A allele.     

Association study of LMP gene polymorphisms in Mexican patients with spondyloarthritis

To evaluate the role of LMP (low molecular weight protein) genes as susceptibility markers for spondyloarthritis (SpA), LMP gene polymorphisms were analyzed in 223 Mexican patients with SpA (81 undifferentiated SpA [U-SpA], 117 with ankylosing spondylitis [AS], 25 with reactive arthritis) and in 139 ethnically matched healthy individuals. LMP genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. The LMP2 and LMP7 allele frequencies were similar in patients and healthy controls. Genotype analysis revealed an increased frequency of LMP2 R/R genotype in the whole group of SpA (pC = 0.003, OR = 2.06, 95%CI = 1.3–3.25) and in the clinical subgroups of AS (pC = 0.039, OR = 1.88, 95%CI = 1.1–3.22) and U-SpA (pC = 0.003, OR = 2.56, 95%CI = 1.37–4.8) compared with healthy controls. Analysis in the LMP7 did not reveal significant differences in patients and healthy controls. The HLA-B27-negative AS subgroup also showed an increased frequency of LMP2 R/R genotype (pC = 0.027, OR = 4.81, 95%CI = 1.21–22.13). The LMP2-R/R AS patients were younger than LMP2-H/R and H/H patients at onset of the disease (16.0 ± 6.8 years for R/R, 22.0 ± 11.2 years for H/R and 28.6 ± 10.9 years for H/H) (p < 0.05). The data suggest that, besides HLA-B27, LMP2 genotypes are also involved in the genetic susceptibility to develop AS in Mexicans. Furthermore, the age at onset of this disease might also be influenced by genotypes of this gene.     

Analysis of a functional BTNL2 polymorphism in type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus

The aim of this study was to test whether the functional variant rs2076530 of the BTNL2 gene confers susceptibility to the autoimmune diseases type 1 diabetes (T1D), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Our study populations consisted of 326 patients with T1D and 351 healthy subjects, 808 patients with RA and 1137 healthy controls, and 372 patients with SLE and 280 healthy controls. Genotyping of the BTNL2 gene rs2076530 polymorphism was performed by real-time polymerase chain reaction technology, using the TaqMan 5′-allele discrimination assay. We observed statistically significant differences in the distribution of BTNL2rs2076530 alleles between patients with T1D, RA, and SLE and healthy controls (p = 0.0035, 0.000003, and 0.00002, respectively), but in two divergent ways: the G allele was associated with T1D and RA, and the A allele was associated with SLE. However, the polymorphism exhibited strong linkage disequilibrium with HLA DQB1–DRB1 haplotypes previously identified as predisposing to the diseases. When the BTNL2 polymorphism was tested conditional on HLA DQB1–DRB1haplotypes, the BTNL2 effect was no longer significant in all three study populations. The BTNL2 rs2076530 polymorphism is associated with T1D, RA, and SLE because of its strong linkage disequalibrium with predisposing HLA DQB1–DRB1 haplotypes in Caucasian populations.     

Correlation of estrogen receptor beta gene polymorphisms with spinal bone mineral density in peri- and post-menopausal Greek women

Estrogens play a significant role in bone physiology. Their action is mainly exerted through their receptors. Estrogen receptor alpha (ER) plays a major role in bone homeostasis and there is evidence suggesting that estrogen receptor beta (ERβ) has also an effect on BMD.

We investigated the possible effect of two ERβ gene polymorphisms on spinal bone mineral density (BMD) and metabolic bone markers in Greek women.

Spine BMD as well as biochemical bone markers were measured in 147 healthy peri- and post-menopausal women [mean age (S.D.) 54 (7.9) years]. Genotyping was performed for two restriction fragment length polymorphisms (RFLPs) of ERβ gene, RsaI in exon 5 and AluI in exon 8. For each polymorphism studied the cohort was divided into two groups: the “wild-type” group (RR and AA, respectively) and the “carrier” group including subjects with at least one allele with the restriction site (Rr&rr and Aa&aa, respectively).

The distribution of RsaI genotypes was RR: 91.2% (n = 134), Rr: 8.2% (n = 12), and rr: 0.6% (n = 1) and of AluI genotypes AA: 36.7% (n = 54), Aa: 57.2% (n = 84), and aa: 6.1% (n = 9). No linkage disequilibrium was found between the two polymorphic sites studied. Spine BMD did not differ significantly in the two groups of either polymorphism, after adjusting for age, weight, height, and years since menopause [mean BMD (S.D.) for RR 0.841 (0.17) g/cm² versus Rr&rr 0.798 (0.13) g/cm², p = 0.25, and mean BMD (S.D.) for AA 0.828 (0.16) g/cm² versus Aa&aa 0.848 (0.17) g/cm², p = 0.32]. No significant differences were noted in metabolic bone markers except for a marginal difference of RR versus Rr/rr in urinary hydroxyproline/creatinine ratio [median (IQR) 3.88 (6.04) μmol/mmol in RR versus 8.2 (4.32) μmol/mmol in Rr/rr, p = 0.05]. Furthermore, no interaction between the two polymorphisms on BMD was found.

In conclusion, in a Greek female post-menopausal population, the two ERβ gene polymorphisms were not associated with BMD, or metabolic bone markers.     

Taq-I polymorphism in 3'UTR of the IL-12B and association with IL-12p40 production from human PBMC

A wide array of studies has demonstrated differences in genotype and allele frequencies of cytokine gene polymorphisms depending on ethnicity and race. In this study, the frequency of Taq-I polymorphism in 3' untranslated region of IL-12B was investigated in two Bulgarian ethnic groups-Bulgarians and Turkish minority. No significant differences of genotype and allele frequencies were observed between these groups. Genotype distribution in the total group of Bulgarian citizens was: AA (61%), CA (32%) and CC (7%), and the allele frequency of 16974 A allele was 0.77. We also evaluated whether this polymorphism affects IL-12p40 production from human PBMC after stimulation. We demonstrated that association between genotype and IL-12p40 production by stimulated PBMC depends on the stimuli used. Our results indicated a significantly decreased IL-12 p40 secretion for the following order of genotypes: AA>CA>CC, after stimulation of PBMC with C3-binding glycoprotein (C3bgp) in contrast to lipopolysaccharide, phytohaemagglutinin and pokeweed mitogen.     

Type 1 diabetes in Jewish Ethiopian immigrants in Israel: HLA class II immunogenetics and contribution of new environment

The interrelationship between human leukocyte antigen immunogenetics and environmental factors and their contribution to the emergence of type 1 diabetes (T1D) were studied in Jewish immigrants from Ethiopia in Israel. This community displays high incidence of T1D, and is unique both by its ethnic segregation and its rapid exposure to a new environment after the immigration. The study population consisted of 152 Ethiopian Jews living in Israel, 33 with T1D and 119 unrelated controls. Human leukocyte antigen class II susceptible and protective alleles in the Jewish Ethiopian patients were similar to those in patients of other ethnic groups in Israel and in non-Jewish Ethiopian patients, with a few exceptions. Three haplotypes were markedly associated with diabetes in Jewish Ethiopian patients: DRB1*0301 DQA1*05 DQB1*02 (OR 4.4, p < 0.001); DRB1*0404 DQA1 03 DQB1*0302 (OR 19.2, p = 0.006), and DRB1*0405 DQA1*03 DQB1*0302 (OR 87.8, p < 0.001). The highly susceptible allele DRB1*0301 was more common in the general Ethiopian population (25.2%) than in all other ethnic groups in Israel, which may render this community prone to the disease. The age at onset of disease in patients with two susceptible haplotypes was negatively correlated with the duration of living in Israel (r = −0.621, p = 0.04). We concluded that ongoing exposure of genetically predisposed immigrants from Ethiopia to diabetogenic environmental factors eventually leads to a high incidence of overt diabetes in this ethnic group.     

Association between interleukin-10 gene -592 C/A polymorphism and the risk of type 2 diabetes mellitus: A meta-analysis of 5320 subjects

Increasing evidence suggests that interleukin-10 (IL-10) gene -592 C/A polymorphism may be associated with an increased risk of type 2 diabetes mellitus (T2DM). To provide a quantitative assessment of the association between this variant and risk of T2DM, we performed this meta-analysis. Systematic searches of electronic databases PubMed, Embase, Web of Science, CBMdisc and CNKI, as well as hand searching of the references of identified articles were performed. A total of 2698 T2DM cases and 2622 controls in seven case-control studies were included in this meta-analysis. The results showed no evidence for significant association between IL-10 gene -592 C/A polymorphism and T2DM risk (for A allele vs. C allele: OR=0.94, 95% CI=0.69-1.29, p=0.69; for A/A vs. C/C: OR=0.88, 95% CI=0.39-1.98, p=0.75; for A/A vs. A/C+C/C: OR=1.04, 95% CI=0.59-1.82, p=0.89; for A/A+A/C vs. C/C: OR=1.11, 95% CI=0.73-1.69, p=0.61). In addition, the similar results were obtained in the subgroup analysis based on the ethnicity. In summary, results from this meta-analysis suggest that the IL-10 gene -592 C/A polymorphism is not associated with T2DM risk.     

Electrode Positioning for Reliable Telemetry ECG Recordings During Social Stress in Unrestrained Rats

We describe a surgical procedure for optimizing the location of telemetry ECG leads in rats. The new location was aimed at obtaining an accurate representation of ECG features throughout the cardiac cycle by limiting the voltage instability usually observed during intense somatomotor activity and improving the signal-to-noise ratio. The two electrodes (wire loops) were fixed on the dorsal surface of the xiphoid process and in the anterior mediastinum close to the right atrium. The implantation procedure was fast, little invasive, and allowed animals to completely recover from intervention. The performance of the “improved” location (IL, n = 10) with respect to two subcutaneous (SC) positionings (“conventional positioning,” CSP, n = 5; “updated location,” USL, n = 5) was evaluated by comparing ECGs obtained in baseline, stress and recovery conditions and during different behavioral activities (immobility and grooming). The resident-intruder test (emotional/physical challenge) was chosen as experimental stress paradigm. The noise level of ECGs obtained from IL rats was lower than in CSP and USL animals, in all recording conditions. Percentages of correctly recognized beats (CRBs) over the total number of beats (TBs) were significantly higher in IL rats than in CSP and USL animals, both in baseline conditions (99% vs. 11% and 40%) and situations involving high somatomotor activity (stress: 97%, 5% and 16%; recovery: 97%, 7%, and 15%) (p < 0.01). The performance of IL as compared to CSP and USL was also better when percentages during grooming and immobility were considered (grooming: 93% vs. 4% and 23%; immobility: 97%, 6%, and 33%; p < 0.01).     

The IL12B 3' untranslated region DNA polymorphism is not associated with early-onset type 1 diabetes

A recent study employing Australian and UK type 1 diabetes families has demonstrated significant transmission bias to affected offspring of a polymorphism (1188A allele; termed allele 1) in the 3' untranslated region (3'UTR) of the interleukin 12B (IL12B) gene which encodes the IL-12p40 subunit of the pro-inflammatory cytokine IL-12. However, results from replication studies in other populations have been controversial. We performed both case-control (n=120 cases; n=330 controls) and family-based (n=307 families) association studies, using the transmission disequilibrium test, to investigate if allele 1 is associated with early-onset type 1 diabetes in Northern Ireland. No association was observed between allele 1 and type 1 diabetes in either case-control (80.8% vs 80.8%; P=0.98) or family-based (49.7% transmissions; P=0.94) studies. Our results do not support earlier reports of an association between allele 1 in the 3'UTR of the IL12B gene and type 1 diabetes.     

Effects of cyclin D1 (CCND1) polymorphism on susceptibility to lung cancer in a North Indian population

Cyclin D1 is involved in normal regulation of the cell cycle and plays an important role in the transition from G1 to S phase of the cell cycle. The CCND1 gene has a G→A polymorphism in exon 4 that increases the frequency of alternate splicing. We analyzed the potential role of CCND1 gene polymorphisms in lung cancer patients (n = 151) and in a matched control population (n = 151). DNA was isolated from blood samples, and exon 4 of CCND1 was amplified by polymerase chain reaction. After digestion with MspI, common CCND1 polymorphic alleles were analyzed by means of agarose gel electrophoresis. The data obtained were analyzed using multiple logistic regression. After adjustment for age, sex, and smoking status, the AG genotype was associated with an increased risk for overall lung cancer (odds ratio OR = 1.7, 95% confidence interval CI = 0.92–3.14). No association was found between AA genotype and risk of lung cancer. In smokers, the combined AG+AA genotypes of CCND1 were found to be significant (OR = 1.9, 95% CI = 1.03–3.71, P = 0.03). No positive association was found between CCND1 genotypes in nonsmokers. The results suggest that the CCND1 A870G gene polymorphisms may increase the risk of lung cancer in smokers from north India.     

The prevalence of menopausal symptoms in a community in Singapore

Objectives: To describe the prevalence and severity of menopausal symptoms experienced by Singaporean women aged 40–60, and to elucidate social and lifestyle factors associated with these symptoms, as well as the average age of menopause. Methods: A population based prevalence survey was carried out on a representative sample of 495 Singaporean women aged 40–60 to determine the prevalence of 17 symptoms commonly associated with the menopause and the mean age of menopause. Results: The participant rate was 69.3%; mean age of participants was 49.0 years (range=40–59 years) with a racial distribution of 84.3% Chinese, 8.3% Malay and 7.4% Indian. Classical menopausal symptoms such as, hot flushes (17.6%), vaginal dryness (20.7%) and night sweats (8.9%) were less commonly reported than somatic symptoms. The most prevalent symptom reported was low backache with aching muscles and joints (51.4%). Perimenopausal women (n=124) experienced a significantly higher prevalence of vasomotor, urogenital and psychological symptoms compared with pre–perimenopausal (n=178) and post–perimenopausal women (n=133). There was no correlation found between menopausal status and somatic symptoms or depression. The mean age of menopause was 49.1 years (range=40–58 years). High educational level was associated with an earlier onset of menopause. Conclusion: The prevalence of classical menopausal symptoms in the local population was low compared with studies on Caucasian women. The mean age of menopause was 49.1 years. This is consistent with findings of other Asian studies.     

MCP-1, RANTES, and SDF-1 polymorphisms in Mexican patients with systemic lupus erythematosus

Chemokines and cytokines play an important role in the inflammatory development and progression of autoimmune diseases. The aim of the present study was to evaluate the role of MCP-1, SDF-1, and RANTES polymorphisms as susceptibility markers for systemic lupus erythematosus (SLE) in a group of Mexican patients. MCP-1-2518, SDF-1 G801A, and RANTES-28 polymorphisms were determined in 242 patients with SLE and 220 ethnically matched healthy controls by the polymerase chain reaction–restriction fragment length polymorphism technique. The differences between patients and healthy controls were evaluated by χ², Fisher’s exact test, and Woolf method for odds ratio. A moderately increased frequency of MCP-1-2518 A allele (p = 0.033, pC = NS) and AA genotype (p = 0.017, pC = NS) existed in SLE patients compared with healthy controls. There was a relationship between polymorphisms and some clinical and laboratory characteristics. SLE patients with and without antiphospholipid syndrome demonstrated different distribution of SDF-1 G801A genotype frequencies. On the other hand, patients with leukopenia, anti-dsDNA, and antiphospholipid autoantibodies demonstrated different MCP-1-2518 genotype distribution compared with patients without these features. Our results suggest that MCP-1 polymorphism is moderately associated with the genetic susceptibility to SLE in Mexican individuals. The polymorphisms could be related to specific clinical and laboratory characteristics in these patients.     

Automated Nucleotide Sequencing Reveals Substantial Disparity Between the HLA-A2 Genes of Bone Marrow Transplant Recipients and Donors

ABSTRACT: HLA disparity is associated with immunological complications after bone marrow transplant and it has been demonstrated that a single amino acid substitution can dramatically alter the function or allorecognition of an HLA molecule. Current serological methods for typing Class I HLA do not distinguish between most HLA-A2 variants which can differ by 1–8 amino acid residues. HLA-A2 disparity between bone marrow transplant patients and donors was investigated using automated nucleotide sequencing of the entire coding region of HLA-A2 genes. A total of 122 HLA-A2 alleles were sequenced from 47 patient-donor pairs (94 individuals). HLA-A2 disparity was observed in 10 of 47 pairs (21.3%) and consisted of HLA-A*0201 mismatched with 0202 (n = 2), 0205 (n = 3), 0206 (n = 3), 0217 (n = 1) or 0221 (n = 1). Four of 6 (66.7%) non-Caucasian or mixed race pairs were HLA-A2 disparate, while 6 of 36 (16.7%) Caucasian pairs were HLA-A2 disparate (p = 0.008). Among all individuals HLA-A*0201 was the most frequently observed allele (90.0%) while 0202 (1.6%), 0205 (2.5%), 0206 (4.1%), 0217 (0.8%) and 0221 (0.8%) were also observed. This study illustrates the diversity of HLA-A2 in non-Caucasian individuals and suggests that HLA-A2 subtyping for applications such as bone marrow transplantation, especially in non-Caucasian or mixed-race donor-recipient pairs, may be important.     

Dietary flour supplementation decreases post-menopausal hot flushes: Effect of soy and wheat

Plants contain compounds with oestrogen — like action called phytoestrogens. Soy contains daidzin, a potent phytoestrogen, and wheat flour contains less potent enterolactones. We aimed to show in 58 postmenopausal women (age 54, range 30–70 years) with at least 14 hot flushes per week, that their daily diet supplemented with soy flour (n = 28) could reduce flushes compared with wheat flour (n = 30) over 12 weeks when randomised and double blind. Hot flushes significantly decreased in the soy and wheat flour groups (40% and 25% reduction, respectively <0.001 for both) with a significant rapid response in the soy flour group in 6 weeks (P < 0.001) that continued. Menopausal symptom score decreased significantly in both groups (P < 0.05). Urinary daidzein excretion confirmed compliance. Vaginal cell maturation, plasma lipids and urinary calcium remained unchanged. Serum FSH decreased and urinary hydroxyproline increased in the wheat flour group.