L O Santos1, R Laranjeira1, M E B de A Borborema1, C G Sotero-Caio1,2, A de R Duarte3, J Araújo4, J de Azevedo Silva1,5, N Santos6. 1. Department of Genetics, Federal University of Pernambuco, Av. da Engenharia, s/n, Cidade Universitária, Recife, Pernambuco, 50740-600, Brazil. 2. Department of Ecology, Faculty of Science, Charles University, Vinicna 7, Praha 2, 128 44, Prague, Czech Republic. 3. Medical Genetic Service, Institute of Integral Medicine Professor Fernando Figueira, Rua dos Coelhos, 300, Boa Vista, Recife, Pernambuco, 50070-050, Brazil. 4. Pediatric Endocrinology Service at Clinical Hospital, Federal University of Pernambuco, Av. da Engenharia, s/n, Cidade Universitária, Recife, Pernambuco, 50740-600, Brazil. 5. Laboratory of Immunopathology Keizo Asami, LIKA, Federal University of Pernambuco, Av. Prof. Moraes Rego, Cidade Universitária, Recife, Pernambuco, 52171-011, Brazil. 6. Department of Genetics, Federal University of Pernambuco, Av. da Engenharia, s/n, Cidade Universitária, Recife, Pernambuco, 50740-600, Brazil. neidesantos.ufpe@gmail.com.
Abstract
PURPOSE: Turner syndrome (TS) patients display considerable immune misregulation, and it is hypothesized that Vitamin D (VTD) activity may fluctuate according to Vitamin D receptor (VDR) polymorphisms and/or expression profile. To uncover a possible relationship between VDR genotype and clinical conditions in TS patients, we investigated two functional VDR variants (Cdx-2 and FokI) for allele and genotype frequencies, as well as expression profile in TS individuals versus healthy controls (HC). METHODS: We performed a genetic association study including 100 TS patients and 116 HC. Genotyping for VDR Cdx-2 G > A (rs11568820) and FokI C > T (rs2228570) was performed using Taqman Genotyping Assays. VDR gene expression was also evaluated in 15 TS and 15 HC, using fluorogenic probes by qPCR. Statistical analyses were performed using nonparametric Mann-Whitney test, with a 5% significance level (p < 0.05) to uncover differences between groups. In addition, we investigated whether shifted VDR mRNA levels were associated with Cdx-2 and FokI variants in TS patients. RESULTS: We detected a significantly higher frequency of T allele (p = 0.006) as well as T/T genotype (p = 0.01) for FokI in TS patients when compared to HC. When assessing VDR expression, we identified a downregulation in TS woman (- 2.84 FC) versus HC (p < 0.001). Furthermore, C/T (11.24 FC; p = 0.01) and T/T (9.20 FC; p = 0.01) FokI genotypes were upregulated when compared to C/C reference genotype. CONCLUSION: TS patients show different distribution of FokI polymorphism. Downregulation of VDR gene expression may contribute to immunological imbalance in TS.
PURPOSE: Turner syndrome (TS) patients display considerable immune misregulation, and it is hypothesized that Vitamin D (VTD) activity may fluctuate according to Vitamin D receptor (VDR) polymorphisms and/or expression profile. To uncover a possible relationship between VDR genotype and clinical conditions in TS patients, we investigated two functional VDR variants (Cdx-2 and FokI) for allele and genotype frequencies, as well as expression profile in TS individuals versus healthy controls (HC). METHODS: We performed a genetic association study including 100 TS patients and 116 HC. Genotyping for VDR Cdx-2 G > A (rs11568820) and FokI C > T (rs2228570) was performed using Taqman Genotyping Assays. VDR gene expression was also evaluated in 15 TS and 15 HC, using fluorogenic probes by qPCR. Statistical analyses were performed using nonparametric Mann-Whitney test, with a 5% significance level (p < 0.05) to uncover differences between groups. In addition, we investigated whether shifted VDR mRNA levels were associated with Cdx-2 and FokI variants in TS patients. RESULTS: We detected a significantly higher frequency of T allele (p = 0.006) as well as T/T genotype (p = 0.01) for FokI in TS patients when compared to HC. When assessing VDR expression, we identified a downregulation in TS woman (- 2.84 FC) versus HC (p < 0.001). Furthermore, C/T (11.24 FC; p = 0.01) and T/T (9.20 FC; p = 0.01) FokI genotypes were upregulated when compared to C/C reference genotype. CONCLUSION: TS patients show different distribution of FokI polymorphism. Downregulation of VDR gene expression may contribute to immunological imbalance in TS.
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