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Response To: Relationship Between Preeclampsia, Gestational Hypertension, And Vitamin D Receptor (VDR) Gene Polymorphisms
Published 2015 · Medicine
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Pathophysiology of preeclampsia, and hence preventive measures are still not elucidated. One hypothesis states that it results from superficial placentation due to immune maladaptation . Vitamin D (1,25(OH)2D), through its immunomodulatory properties, has been shown to control these adverse immune reactions [2, 3]. It has an important role in promoting a shift from Th1 to a Th2-dominated pattern in immune response which is favourable for pregnancy [4, 5]. Observational studies on relation between vitamin D status during pregnancy and preeclampsia have not shown consistent associations . Many, including ours have shown association between vitamin D deficiency and preeclampsia . Recent randomized control trial by Hollis et al. indicates monotonic reductions in risk for preeclampsia with increasing supplement dosage (400, 2000, 4000 IU), which was significant after controlling for race . The difference in these observations across different geographical areas and different races may be due to racespecific allelic frequencies in the vitamin D receptor (VDR) gene . The VDR gene is located on chromosome 12 at q11–q13 . It is a high-affinity ligand-activated transcription factor. Once bound to its ligand, it heterodimerizes with the retinoid X receptor (RXR). This complex recognizes vitamin D response elements in the target genes and affects the gene transcription. Deleterious mutations in the VDR gene can cause vitamin D-resistant rickets. Subtle sequence variations [single nucleotide polymorphisms (SNPs)] occur more frequently . A polymorphism is a genetic variant that appears in at least 1 % of the population. Polymorphic variations in the 50-promoter of the VDR gene can affect mRNA expression patterns and levels, while those in 30 untranslated region (UTR) can affect the mRNA stability and protein translation efficiency. The interpretation of polymorphic variations in this gene is challenging as the few polymorphisms that have been studied are mostly anonymous restriction fragment length polymorphisms (RFLP), i.e. have an unknown functional effect. These anonymous polymorphisms are linked to actually functional polymorphisms elsewhere in the same or a nearby gene. Thus, it is important to understand how different polymorphisms relate to each other, both at genetic and at functional level . The association of alleles of different polymorphisms with each other within a population is called linkage disequilibrium (LD) . This means that presence of certain allele can be predicted by the presence of an adjacent linked one. In cases of high levels of LD, this leads to blocks of alleles that are present together forming a haplotype. Polymorphism within each block showed little, if any, LD with polymorphisms in a different block . Vitamin D is regarded as a potent endocrine suppressor of renin biosynthesis to regulate the renin-angiotensin system . In cell cultures, 1,25(OH)2D directly suppressed renin gene transcription by a VDR-dependent mechanism. Genetic variation at the FokI (rs2228570) polymorphism of the VDR is associated with plasma renin This reply refers to the comment available at doi:10.1007/s00404-015-3797-8.