Hypertension and osteoporosis are chronic diseases that, until complications occur, are mostly asymptomatic. In addition to several environmental risk factors, both diseases are also characterized by genetic influences. Vascular endothelial growth factor (VEGF) is a signaling protein from the cystine knot growth factor family, which also includes VEGF-B, VEGF-C, VEGF-D, and placental growth factor. VEGF plays an important role in the formation of new blood vessels during development, physiological processes in adults, and pathology of certain diseases. The effect of VEGF on bone mineral density (BMD) and the development of osteoporosis has not yet been precisely defined. Research data suggest that physiological VEGF circulating levels help to maintain bone regeneration homeostasis, whereas low or high VEGF levels lead to increased bone degradation and osteoporosis. An association between VEGF and high blood pressure can be observed in anti-VEGF therapy. A common side effect of drugs that inhibit VEGF and its signaling pathways is high blood pressure, which occurs in at least a quarter of treated patients.
We aimed to determine the influence of rs4416670, rs6921438, rs6993770, and rs10738760 polymorphisms on BMD and high blood pressure. Genome-wide association studies have shown that selected polymorphisms are responsible for approximately 50 % of the variability in serum circulating VEGF levels. The polymorphisms rs4416670 and rs6921438 are located on chromosome 6p21.1 near the VEGF gene. The rs6993770 polymorphism is located on chromosome 8q23.1 in the ZFPM2 gene, while the rs10738760 polymorphism is located on chromosome 9p24.2 near the VLDLR and KCNV2 genes. In 315 postmenopausal women, the genotypes of selected polymorphisms were determined from isolated DNA samples using real-time polymerase chain reaction (qPCR). The influence of selected polymorphisms on BMD and osteoporosis was determined by statistical analysis, as well as the connection between selected polymorphisms and high blood pressure in postmenopausal women.
TT (wild-type homozygotes) of rs4416670 polymorphism were found to be more frequent (p = 0.04) in the group of women with osteoporosis compared to the osteopenia group and group of healthy postmenopausal women. Compared to the combined genotypic subgroups CT and CC (mutated homozygotes), genotypic subgroup TT of rs4416670 polymorphism also negatively affected BMD of the trochanter (p = 0.035), intertrochanter (p = 0.025) and hip (p = 0.022) in all postmenopausal women. Genotype subgroup AA (mutated homozygotes) of rs6921438 polymorphism had significantly higher BMD of the femoral neck (p = 0.031) and intertrochanter (p = 0.029) in comparison to genotype GG (wild type). For this polymorphism we also found a significantly lower BMD of the trochanter (p = 0.019), intertrochanter (p = 0.028) and hip (p = 0.017) in the GG genotype group of healthy women compared to combined subgroups AG and AA. Based on the obtained results, we conclude that the polymorphisms rs4416670 and rs69214380 in postmenopausal subjects affect BMD and consequently the risk of osteoporosis. Polymorphisms rs6993770 and rs10738760 do not affect BMD or osteoporosis. There was no effect of selected polymorphisms on high blood pressure.
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