Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2.

We and others have previously reported linkage to schizophrenia on chromosome 10q25-q26 but, to date, a susceptibility gene in the region has not been identified. We examined data from 3606 single-nucleotide polymorphisms (SNPs) mapping to 10q25-q26 that had been typed in a genome-wide association study (GWAS) of schizophrenia (479 UK cases/2937 controls). SNPs with P<0.01 (n=40) were genotyped in an additional 163 UK cases and those markers that remained nominally significant at P<0.01 (n=22) were genotyped in replication samples from Ireland, Germany and Bulgaria consisting of a total of 1664 cases with schizophrenia and 3541 controls. Only one SNP, rs17101921, was nominally significant after meta-analyses across the replication samples and this was genotyped in an additional six samples from the United States/Australia, Germany, China, Japan, Israel and Sweden (n=5142 cases/6561 controls). Across all replication samples, the allele at rs17101921 that was associated in the GWAS showed evidence for association independent of the original data (OR 1.17 (95% CI 1.06-1.29), P=0.0009). The SNP maps 85 kb from the nearest gene encoding fibroblast growth factor receptor 2 (FGFR2) making this a potential susceptibility gene for schizophrenia.

Dietary and hormonal interrelationships among vegetarian Seventh-Day Adventists and nonvegetarian men.

The relationship between dietary nutrients and plasma testosterone, 5 alpha-dihydrotestosterone, estradiol-17 beta, luteinizing hormone, and prolactin levels was investigated in 12 Seventh-Day Adventist (SDA) vegetarian (SV), 10 SDA nonvegetarian (SNV), and 8 non-SDA nonvegetarian (NV) men. Fasting blood samples and 3-day dietary intake information were obtained from each subject. The SV subjects consumed significantly more crude and dietary fiber than the SNV and NV subjects, respectively. Plasma levels of testosterone and estradiol-17 beta were significantly lower in the SV than in the omnivores. Additionally, the plasma levels of testosterone and estradiol-17 beta of the combined groups (SV, SNV, and NV) revealed a significant negative relationship with their crude and dietary fiber intakes. These subjects hormonal milieu was related to specific dietary constituents, possibly leading to a decreased plasma concentration of androgen and estrogen in vegetarians. Implications include the possible modification of prostate cancer risk through dietary intervention.

Effect of low- and high-fat intakes on the hormonal milieu of premenopausal women.

To compare the influence of low- and high-fat diets on hormone metabolism, we studied six premenopausal women over two complete menstrual cycles. After an initial 7-10 d dietary adjustment subjects were randomly assigned to either low- (25% of calories) or high-fat (46% of calories) diets. The diets were isocaloric and similar in proportions of protein, polyunsaturated:saturated fatty acid ratio, fiber, and cholesterol. All subjects completed both diets in a crossover experimental design. Fasting blood and 24-h urine samples were collected every other day. No significant differences in plasma luteinizing hormone, progesterone, prolactin, estrone (E1), and estradiol-17 beta (E2) or in urinary E1, E2, and estriol were observed. Prolactin secretion in response to thyrotropin-releasing hormone stimulation was also unchanged. Dietary fat may influence breast-cancer incidence by modulating the hormonal environment; however, an increase in short-term fat intake from 28 to 51 g/1000 kcal did not lead to substantial differences in the hormonal milieu.

Dietary and hormonal interrelationships in premenopausal women: evidence for a relationship between dietary nutrients and plasma prolactin levels.

To investigate possible differences in tissue exposures to reproductive hormones and to determine hormone-nutrient interrelationships, we studied 10 vegetarian and 10 nonvegetarian premenopausal Seventh-day Adventist women. Over 3 d in each of three consecutive menstrual cycles, we collected diet records, fasting midluteal phase blood, and 24-h urine samples. During each study period, we measured plasma and urinary estrogens, plasma free and protein bound-estradiol-17 beta, the binding capacity of sex-hormone-binding globulin (SHBG), androgens, progesterone, and prolactin levels. The omnivores consumed significantly more protein, total and saturated fatty acids, oleic and linoleic acids, and cholesterol than did the vegetarians. Hormonal status and binding capacity of SHBG were similar in both groups. However, for nonvegetarians, prolactin levels were positively correlated with dietary energy, protein, total and saturated fatty acids, and oleic acid. Further study delineating the effects of specific dietary nutrients on the basal level of prolactin secretion is warranted.

In vitro binding of steroid hormones by natural and purified fibers.

The in vitro binding of estrone, estradiol-17 beta, estriol, testosterone, dihydrotestosterone, and estrone-3-glucuronide by wheat, oat, and corn brans, oat hulls, cellulose, lignin, and cholestyramine resin was measured. The extent of steroid sequestration was characteristic and reproducible for each hormone. Cholestyramine bound an average of 90% of all the steroids tested, whereas cellulose bound the least (12%). Of the other substances tested, each bound the following percentage of unconjugated hormones: lignin, 87%; wheat and oat brans, 45% each; corn bran 44%; and oat hulls, 32%. The conjugated steroid was less likely to bind than the unconjugated steroids. Lignin appeared to be an important component in the interaction with steroid hormones. The results support the hydrophobic nature of adsorption and suggest that the components of fiber in diet should be considered separately when evaluating in vivo metabolic effects.