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      The Relationship of Target Organ Damage and 24-Hour Ambulatory Blood Pressure Monitoring with Vitamin D Receptor Gene Fok-I Polymorphism in Essential Hypertension

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          Background: The contribution of genetic factors in hypertension cannot be denied. Methods: In this study we evaluated the relationship between vitamin D receptor (VDR) gene polymorphisms ( Bsm-I, Apa-I and Fok-I), and target organ damage in 74 patients (female/male 49/25, mean age 49.2 ± 8 years) with essential hypertension. The VDR genotypes were evaluated by polymerase chain reaction and digestion of the amplified products by related enzymes. Patients with diabetes mellitus or impaired glucose tolerance and severe obesity were excluded. All patients underwent a complete physical examination, full biochemistry and urinalysis; in addition, all of them were assessed for target organ damage. Twenty-four-hour ambulatory blood pressure monitoring was performed in all patients. Results: No significant difference was detected in biochemistry results and physical examination between groups for Bsm-I and Apa-I VDR gene polymorphisms. Patients were distributed as FF (n = 39) and non-FF (Ff/ff, n = 35) for Fok-I polymorphism. A negative correlation was present between vitamin D levels and day-time interval and early morning average by the measurement of 24-hour ambulatory blood pressure in the non-FF group. Serum cystatin-C was higher in the non-FF group (p = 0.012). In addition on retinal examination, the degree and presence of retinopathy were significantly higher in the non-FF group when compared to the FF group (p = 0.025, p = 0.018, respectively). Conclusion: Knowing the VDR gene polymorphisms status may be helpful in preventing target organ damage in hypertensive patients.

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          Most cited references 21

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          A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women.

          The effect of a T-C transition polymorphism at the translation initiation codon of the human vitamin D receptor (VDR) gene on the biological function of the encoded protein was investigated. Of 239 Japanese women volunteers subjected to genotype analysis for this polymorphism, 32 (13%) were genotype MM (the M allele is ATG at the putative translation start site), 75 (31%) were genotype mm (the m allele is ACG at the putative translation start site), and 132 (55%) were genotype Mm. The bone mineral density (BMD) in the lumbar spine (L2-L4) was determined for 110 healthy premenopausal women from the volunteers and was shown to be 12.0% greater (p < 0.05) for mm homozygotes than for MM homozygotes. Synthesis of the proteins by the M and m alleles from the cloned cDNAs in vitro and in transfected COS-7 cells revealed them to have a size of 50 and 49.5 kD, respectively, as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. This size difference is consistent with initiation of translation of the M allele-encoded protein from an ATG codon located at nucleotides +10 to +12 in the conventional open reading frame. The extent of vitamin D-dependent transcriptional activation of a reporter construct under the control of a vitamin D response element in transfected HeLa cells was approximately 1.7-fold greater for the m type VDR than for the M type protein. These results suggest that the polymorphism at the translation start site of the VDR gene may modulate BMD in premenopausal Japanese women.
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            Cloning and expression of full-length cDNA encoding human vitamin D receptor.

            Complementary DNA clones encoding the human vitamin D receptor have been isolated from human intestine and T47D cell cDNA libraries. The nucleotide sequence of the 4605-base pair (bp) cDNA includes a noncoding leader sequence of 115 bp, a 1281-bp open reading frame, and 3209 bp of 3' noncoding sequence. Two polyadenylylation signals, AATAAA, are present 25 and 70 bp upstream of the poly(A) tail, respectively. RNA blot hybridization indicates a single mRNA species of approximately equal to 4600 bp. Transfection of the cloned sequences into COS-1 cells results in the production of a single receptor species indistinguishable from the native receptor. Sequence comparisons demonstrate that the vitamin D receptor belongs to the steroid-receptor gene family and is closest in size and sequence to another member of this family, the thyroid hormone receptor.
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              Plasma concentrations of cystatin C in patients with coronary heart disease and risk for secondary cardiovascular events: more than simply a marker of glomerular filtration rate.

              Renal impairment (RI) is associated with worse prognosis. Recently, cystatin C has been shown to represent a potentially superior marker of the glomerular filtration rate compared with creatinine clearance (CrCl). We evaluated the impact of cystatin C and other markers of RI on prognosis in a large cohort of patients with coronary heart disease (CHD). Cystatin C, creatinine (Cr), and CrCl were determined at baseline in a cohort of 1033 patients (30-70 years) with CHD. Patients were followed for a mean of 33.5 months, and a combined endpoint [fatal and nonfatal cardiovascular disease (CVD) events] was used as the outcome variable. Cystatin C was measured by immunonephelometry, and CrCl was calculated. During follow-up, 71 patients (6.9%) experienced a secondary CVD event. Neither Cr (P = 0.63) nor CrCl (P = 0.10) were associated with incidence of CVD events, whereas cystatin C was clearly associated with risk of secondary CVD events (P <0.0001). In multivariate analyses, patients in the top quintile of the cystatin C distribution at baseline had a statistically significantly increased risk of secondary CVD events even after adjustment for classic risk factors, severity of coronary disease, history of diabetes mellitus, treatment with angiotensin-converting enzyme inhibitors, and C-reactive protein (hazard ratio, 2.27; 95% confidence interval, 1.05-4.91) compared with patients in the bottom quintile. These data support the possibly important prognostic value of cystatin C among patients with known CHD and suggest that it may be a useful clinical marker providing complementary information to established risk determinants.

                Author and article information

                Kidney Blood Press Res
                Kidney and Blood Pressure Research
                S. Karger AG
                January 2007
                16 January 2007
                : 29
                : 6
                : 344-350
                Departments of aNephrology, bMedical Genetics, cBiochemistry, dOphthalmology, and eInternal Medicine, Zonguldak Karaelmas University School of Medicine, Zonguldak, Turkey
                97409 Kidney Blood Press Res 2006;29:344–350
                © 2006 S. Karger AG, Basel

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                Tables: 4, References: 33, Pages: 7
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