The APOB gene polymorphism in the pathogenesis of gallstone disease in pre- and postmenopausal women.

AIM OF THE STUDY: The decrease in estrogen levels in the postmenopausal period changes the lipid profile by the expression of hepatic genes related to metabolism of cholesterol and bile acid synthesis that could be important in the pathogenesis of cholelithiasis. The aim of the study was to determine the APOB gene 7673C>T and 12669G>A polymorphisms in the pathogenesis of gallstones and analysis of the composition of gallstones in pre- and postmenopausal women. MATERIAL AND METHODS: The study group consisted of 94 women qualified to the laparoscopic cholecystectomy while the control group consisted of 81 women in whom gallstones and other changes in the bile ducts were excluded. Gallstones composition analysis was performed using commercially available assays. The prevalence of the APOB gene polymorphisms was determined using the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS: When assessing the composition of gallstones in pre- and postmenopausal women, we observed differences in the studied parameters. Analysis of genetic variants of APOB gene 7673C>T and 12669G>A polymorphisms showed no significant statistical differences between studied groups and controls. CONCLUSIONS: Analysis of 7673C>T and 12669G>A polymorphisms showed no relationship between specific genetic variants and the risk of gallstones in pre- and postmenopausal women, pointing to the fact that the investigated polymorphisms are not relevant as prognostic factors in gallstone disease in the Caucasian population. Because of the possible contribution of a variety of factors in gallstones pathogenesis the studies are required to take account of additional environmental factors, what may indicate different occurrence between investigated polymorphisms, gallstone disease development and gallstones composition in Caucasians.

The importance of G2677T/A and C3435T polymorphisms of the MDR1 gene in the aetiology of colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is the most common cancer among patients, and its aetiology is still not precisely known. It is believed that 15-30% of colorectal cancers are genetically determined. P-glycoprotein (P-gp) encoded by the MDR1 gene in normal conditions plays an important role in the action of colon epithelial cells. However, the MDR1 polymorphism influences the P-gp expression and can weaken its effect against xenobiotics (procarcinogens) and increase the frequency of CRC. AIM: To evaluate the correlation between the MDR1 C3435T and G2677T/A polymorphisms and the risk of colorectal cancer. MATERIAL AND METHODS: The study group with colorectal cancer included 47 women and 60 men while the control group consisted of 110 healthy patients. The diagnosis in patients suffering from CRC was confirmed by histopathological report. Genetic analysis was performed using PCR-RFLP method. RESULTS: We showed only a correlation between the frequency of CT and TT genotypes of C3435T polymorphism and the risk of colorectal cancer in younger age. There was no correlation between the C3435T and G2677T/A polymorphisms of the MDR1 gene and other clinical parameters. CONCLUSIONS: Our findings suggest that T allele carriers of C3435T polymorphism have an increased risk of CRC. However, further studies are needed on a much larger number of patients and genes associated with metabolism and transport of xenobiotics including procarcinogens.

[Osteoporosis in thyroid diseases]. / Osteoporoza w chorobach tarczycy.

Thyroid hormones play the essential role in the regulation of metabolism and bone remodeling in physiological conditions and in the course of thyroid dysfunction. Introduction of densitometry to the diagnostics of osteoporosis has made possible the evaluation of influence of both hyperthyroidism and hypothyroidism and their treatment on bone mineral density. Moreover it became possible to estimate the influence of treatment with exogenous thyroid hormones on the skeletal system. Authors presented mechanisms of the thyroid hormones action on bone tissue and analysed current state of knowledge concerning the influence of the thyroxine treatment with replacement and suppressive doses on the bone mineral density. The influence of thyroid hormones on the skeletal system with respect to premenopausal and postmenopausal period was also discussed. Great discrepancies in literature data and its reasons were underlined.

[The influence of treatment with substitutive or suppressive doses of thyroxine on biochemical bone turnover markers]. / Wplyw leczenia substytucyjnymi i supresyjnymi dawkami tyroksyny na zachowanie sie markerów przebudowy kostnej.

PURPOSE: Thyroid hormones belong to essential regulators of growth and remodelling of bones. The development of modern radioimmunological and immunoenzymatic methods opened the way to studies on the influence of exogenous thyroxine on the metabolism of osseous tissue. The activity of osteoblasts and the osteoclast ratio is a measure of the process termed "bone turnover" which can be assessed by determining concentrations of enzymes and bone matrix proteins in serum. The aim of this study was to evaluate the influence of a twelve-month regimen with substitutive or suppressive doses of thyroxine on bone alkaline phosphatase (BAP) concentrations in serum and deoxypyridoline (DPR) concentrations in the urine of women with hypothyroidism or with simple goitre. MATERIAL AND METHODS: We enrolled 26 women with not-treated hypothyroidism (Group I) and 41 with not-treated simple goitre (group II). The age of the patients ranged from 29 to 66 years. Patients were qualified for treatment with substitutive (hypothyroidism) or suppressive (goitre) doses of thyroxine. Each group was divided into two subgroups: IA--15 premenopausal patients with hypothyroidism (mean age 41.53 +/- 1.39 years); IB--11 postmenopausal patients with hypothyroidism (mean age 53.18 +/- 1.66 years); IIA--24 premenopausal patients with simple goitre (mean age 39.71 +/- 0.98 years); IIB--17 postmenopausal patients with simple goitre (mean age 53.82 +/- 1.35 years). Evaluations of bone turnover markers in serum (BAP) and in twenty-four hour urine collection (DPR) and serum concentrations of TSH, FT3 and FT4 were carried out prior to treatment and after 1, 3, 6, 9 and 12 months ofthyroxine administration. RESULTS: Bone turnover markers increased during treatment with substitutive or suppressive doses of thyroxine, especially in postmenopausal women. CONCLUSIONS: 1. Treatment with substitutive or suppressive doses of thyroxine stimulates osteogenic and osteoclastic processes in pre- and postmenopausal women. 2. Suppressive doses of thyroxine are more potent in increasing bone turnover than substitutive doses. 3. The osteoclastic process is more intense in postmenopausal women on substitutive or suppressive doses of thyroxine.