Association between vitamin D receptor gene polymorphisms (Fok I, Cdx-2) and bone mineral density in Slovak postmenopausal women.

Osteoporosis is a skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue with consequent increase in bone fragility and fracture risk. Bone mineral density (BMD), the major determinant of osteoporotic fracture risk, has a particular genetic background. Vitamin D receptor (VDR) is implicated in the regulation of bone mineral density. The present study evaluates the association between Vitamin D receptor gene polymorphisms Fok I (rs2228570), Cdx-2 (rs11568820), bone mineral density and fracture risk in Slovak postmenopausal women. A total of 403 unrelated Slovak postmenopausal women aged 43-86 years were genotyped using TaqMan®SNP Genotyping Assays. Lumbar spine, femoral neck and total hip BMD/T-score were detected by dual energy X-ray absorptiometry (DEXA). We found the Fok I and Cdx-2 polymorphism in the VDR gene to be associated with osteoporotic fractures (non-vertebral fractures: Fok I p = 0.001; Cdx-2 p = 0.0000; all fractures: Fok I p = 0.0001; Cdx-2 p = 0.0000) (Fok I: OR = 0.50, 95% CI = 0.35-0.71; Cdx-2: OR = 0.25, 95% CI = 0.17-0.37). The present data suggest that VDR gene Fok I and Cdx-2 polymorphisms contribute to the determination of BMD in Slovak postmenopausal women and can probably be used with other genetic markers together to identify individuals at high risk of osteoporosis.

Increased thyroid volume and frequency of thyroid disorders signs in schoolchildren from nitrate polluted area.

Thyroid volume (ThV) and echogenicity by ultrasound were estimated in 324 schoolchildren (aged between 10 and 13-years) from high nitrate area (HNA) located in agricultural lowland with high nitrate drinking water supply (51-274 mg/l) from shallow wells. The data were compared to children of the same age from low nitrate area (LNA) consisting of 168 children from the neighboring area with very low nitrate (< 2 mg/l) drinking water and of 596 children from the city of Kosice located in a vicinity of LNA and also supplied by low nitrate water. Blood samples were obtained from 315 willing children from HNA and 109 children from LNA and the levels of thyrotropin (TSH), total thyroxine (TT4), free triiodothyronine (FT3) and thyroperoxidase antibodies (anti-TPO) in serum were determined. ThV (mean +/- SE) in 10-year (5.10 +/- 0.14 ml) and 13-year (5.97 +/- 0.11 ml) old children from HNA was significantly higher than that in two groups of respective age from LNA, 4.58 +/- 0.17 (p < 0.02) and 5.23 +/- 0.15 ml (p < 0.05), and from the city of Kosice, 4.77 +/- 0.10 ml (p < 0.05) and 4.87 +/- 0.1 0ml (p < 0.0001). The frequency of hypoechogenicity in HNA was also significantly higher than that in pooled LNA plus Kosice, 13.7% vs. 4.7% (p < 0.01) in 10-year and 10.6% vs. 5.7% (p < 0.03) in 13-year, respectively. The frequency of TSH level in the range of subclinical hypothyroidism (> 4.0 mU/l) in pooled age groups from HNA was 13/324 (4.0%) and that of positive anti-TPO was 8/324 (2.5%), while no case of either increased TSH or positive anti-TPO was found in 109 children from LNA. Finally, no differences in the levels of TT4 and FT3 were found between HNA and LNA. It was concluded that long-term exposure to high nitrate intake by drinking water and home made meals from local products results in increased thyroid volume and increased frequency of signs of subclinical thyroid disorders (thyroid hypoechogenicity by ultrasound, increased TSH level and positive anti-TPO).

TNFRSF11B gene polymorphisms, bone mineral density, and fractures in Slovak postmenopausal women.

Osteoporosis is a common disease that is characterized by low bone mineral density (BMD), deterioration in bone microarchitecture, and increased fracture risk. Due to its important role in bone biology, the TNFRSF11B gene, coding for OPG, has been considered as a candidate gene for osteoporosis. In this study, single nucleotide polymorphisms (SNPs) A163G, T245G, and G1181C (rs3102735, rs3134069, and rs2073618, respectively) within the TNFRSF11B gene were studied for association with BMD and fracture incidence in a cohort of 327 postmenopausal Slovak women. Genomic DNA was extracted and purified from peripheral blood leukocytes by the commercial kit JetQuick (Genomed GmbH, Germany) using a standard protocol. Genotyping was performed using the Custom TaqMan® SNP Genotyping Assays. The lumbar L1-L4 spine BMD (g/cm(2)) and T-score in the subgroup of Slovak postmenopausal women with osteoporotic fractures were significantly lower than those in the subgroup of women without fracture (p = 0.0025; p = 0.0009). We identified the T245G (rs3134069) polymorphism in the TNFRSF11B gene associated with osteoporotic fractures (vertebral fractures: p = 0.0320; non-vertebral fractures: p = 0.0005; all fractures: 0.0000). The polymorphism T245G (rs3134069) in the TNFRSF11B gene could be used together with other genetic markers to identify individuals at high risk of osteoporotic fractures. The results from the present study provided more evidence to reveal the role of TNFRSF11B gene polymorphisms in BMD and the risk of osteoporotic fractures.