Association of multiple nucleotide variations in the pituitary glutaminyl cyclase gene (QPCT) with low radial BMD in adult women.

Correlation between 13 genetic variations of the glutaminyl-peptide cyclotransferase gene and adjusted aBMD was tested among 384 adult women. Among 13 variations with strong linkage disequilibrium, R54W showed a prominent association (p = 0.0003), which was more striking when examined among 309 elder subjects (> or =50 years; p = 0.0001). Contribution for postmenopausal bone loss was suggested. INTRODUCTION: Alterations in homeostatic regulation of estrogen through the hypothalamus-pituitary-gonadal axis (HPG axis) importantly affect the pathogenesis of osteoporosis. Osteoporosis-susceptibility genes have been proposed in this hormonal axis, such as estrogen receptor genes and the gonadotropin-releasing hormone gene (GnRH). Here we report another example of genes: glutaminyl-peptide cyclotransferase gene (QPCT), an essential modifier of pituitary peptide hormones, including GnRH. MATERIALS AND METHODS: Analyses of association of 13 single nucleotide polymorphisms (SNPs) at the QPCT locus with adjusted areal BMD (adj-aBMD) were carried out among 384 adult women. Linkage disequilibrium (LD) was analyzed by haplotype estimation and calculation of D' and r2. Multiple regression analysis was applied for evaluating the combined effects of the variations. RESULTS AND CONCLUSIONS: LD analysis indicated strong linkage disequilibrium within the entire 30-kb region of the QPCT gene. Significant correlations were observed between the genotypes of the six SNPs and the radial adj-aBMD, among which R54W (nt + 160C>T) presented the most prominent association (p = 0.0003). Striking association was observed for these SNPs among the 309 subjects >50 years of age (R54W, p = 0.0001; -1095T>C, p = 0.0002; -1844C>T, p = 0.0002). Multiple regression analyses indicated that multiple SNPs in the gene might act in combination to determine the radial adj-aBMD. These results indicate that genetic variations in QPCT are the important factors affecting the BMD of adult women that contribute to susceptibility for osteoporosis. The data should provide new insight into the etiology of the disease and may suggest a new target to be considered during treatment.     

Primary adrenocortical tumors in autopsy records —A survey of “cumulative reports in Japan” from 1973 to 1984—

All cases of primary adrenocortical tumors, including those found incidentally, recorded in the Pathological Autopsy Case Annuals of Japan during a 12 year period from 1973 to 1984 were surveyed. Age- and sex-specific incidences of lesions were estimated from the population, mortality and autopsy statistics for the same period. There were 101 adenomas, 77 of which were presumed to be non-functional, and 222 carcinomas. The age-specific distribution profiles of both the benign and malignant tumors showed single peaks in the sixties and could not be distinguished from one another. The estimated age-specific distribution of morbidity of the non-functional adenomas showed a peak at about 10 years younger than that found in the autopsy records, although it was again similar to that of carcinoma derived from various clinical reports. The morbidity of the non-functional adenomas per 100,000 population was almost equal to that of breast cancer in Japan, being highest in the fifties age group with more than 4,000 people a year being suggested to have adenoma in this age bracket.     

Rat atrial natriuretic polypeptide increases net water, sodium and chloride absorption across rat small intestine in vivo

Localization of binding sites for synthetic rat atrial natriuretic polypeptide (alpha-rANP) and the effect of the peptide on net water and electrolyte movement in vivo perfused small intestine of the rat were studied. Autoradiographic study demonstrated that specific binding sites were localized on a space between the base of epithelia and lamina propria of the small intestine. Alpha-rANP (0.25 micrograms/min) infused into the superior mesenteric artery of rats increased net absorption of water (46% increase in comparison with controls), Na (84% increase) and Cl (70% increase) across the small intestinal tract perfused with Ringer's solution. These increases were also observed when glucose-free Ringer's solution was employed. Thus it would be concluded that the Na-glucose cotransport system is not involved in the action of alpha-rANP. These observations suggest that alpha-rANP controls circulating water-electrolyte balance through regulating not only renal function but also intestinal water, Na and Cl absorption.