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Molecular and clinical analysis of TRPC6 and AGTR1 genes in patients with pulmonary arterial hypertension.

Pousada G, Baloira A, Valverde D - Orphanet J Rare Dis (2015)

Bottom Line: We used a non-parametric test to determine if significant differences were found between the groups studied and chi-square test to compare clinical and hemodynamic variables among genotypes.Several clinical and hemodynamic parameters showed significant differences between carriers and non-carriers of these single nucleotide polymorphisms (SNPs).This study seems to suggest that c.1-361A > T, c.1-254C > G and c.1-218C > T polymorphisms in TRPC6 gene and c.1166A > C polymorphism in AGTR1 could have a role in the development of this disease.

View Article: PubMed Central - PubMed

Affiliation: Department Biochemistry, Genetics and Immunology, Faculty of Biology, University of Vigo, Campus As Lagoas Marcosende S/N, 36310, Vigo, Spain. g.pousada@uvigo.es.

ABSTRACT

Background: Pulmonary arterial hypertension (PAH) is a rare and progressive vascular disorder characterized by increased pulmonary vascular resistance and right heart failure. The aim of this study was to analyze 5'UTR region in canonical transient receptor potential isoform 6 (TRPC6) and 3'UTR region in Angiotensin II type I receptor (AGTR1) genes in patients with idiopathic and associated PAH. Correlation among mutations and clinical and functional parameters was further analyzed.

Methods: Analysis of TRPC6 and AGTR1 genes was performed by polymerase chain reaction (PCR) and direct sequencing. We used a non-parametric test to determine if significant differences were found between the groups studied and chi-square test to compare clinical and hemodynamic variables among genotypes.

Results: Fifty five patients and fifty two controls were included in this study. We found statistically significant differences for c.1-361A > T (p = 0.0077), c.1-254C > G (p < 0.0001) and c.1-218C > T (p = 0.0021) in TRPC6 gene and c.1166A > C (p < 0.001) in AGTR1 gene, between patients and controls. Idiopathic PAH patients (IPAH) and controls presented significant differences for all 3 TRPC6 polymorphisms (p = 0.020), (p = 0.002) and (p = 0.008) respectively, and also showed differences for AGTR1 gene (p < 0.001). In associated PAH (APAH) patients we found statistical differences for c.1-254C > G (p < 0.001) and c.1-218C > T (p = 0.001) in TRPC6 gene and c.1166A > C (p = 0.001) in AGTR1 gene. Several clinical and hemodynamic parameters showed significant differences between carriers and non-carriers of these single nucleotide polymorphisms (SNPs). Nineteen patients were carriers of all 3 SNPs in TRPC6 gene and presented a more severe phenotype with differences in mean pulmonary arterial pressure (p = 0.016), systolic pulmonary arterial pressure (p = 0.040), cardiac index (p < 0.001) and 6 minute walking test (p = 0.049). 16 of these patients harbored the SNP in AGTR1 gene. These patients showed differences in age at diagnosis (p = 0.049), mean pulmonary arterial pressure (p = 0.033), cardiac index (p = 0.002) and 6 minute walking test (p = 0.039).

Conclusions: PAH is a rare disease with pulmonary vascular remodeling caused in part by a heterogeneous constellation of genetic arrangements. This study seems to suggest that c.1-361A > T, c.1-254C > G and c.1-218C > T polymorphisms in TRPC6 gene and c.1166A > C polymorphism in AGTR1 could have a role in the development of this disease.

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Genetic disposition between PAH patients (blue) and controls (orange) for eachTRPC6SNPs. A: c.1-361; B: c.1-254; C: c.1-218.
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Fig3: Genetic disposition between PAH patients (blue) and controls (orange) for eachTRPC6SNPs. A: c.1-361; B: c.1-254; C: c.1-218.

Mentions: We found statistically significant differences between patients and controls (p = 0.0077) for TRPC6 c.1-361A > T polymorphism (Figure 2). TT genotype was present in 2 patients (3.7%) but in any control; AT genotype was also more frequent in patients (52%) than controls (31%), whose most common genotype was AA. These results are shown in Figure 3a. Patients showed an allele frequency of 0.690 for A and 0.303 for T, but this frequency was 0.836 for A and 0.163 for T in controls. Patients with this polymorphism were not in Hardy-Weinberg Equilibrium (H-WE) with p = 0.0085 but controls were in H-WE with p = 0.1588. The predominant genotype for IPAH patients was AT (61%) and for APAH patients was AA (50%) (Figure 4a). Comparing the distribution of this polymorphism, in healthy people reached statistically differences with IPAH (p = 0.02), but not with APAH (p = 0.097).Figure 2


Molecular and clinical analysis of TRPC6 and AGTR1 genes in patients with pulmonary arterial hypertension.

Pousada G, Baloira A, Valverde D - Orphanet J Rare Dis (2015)

Genetic disposition between PAH patients (blue) and controls (orange) for eachTRPC6SNPs. A: c.1-361; B: c.1-254; C: c.1-218.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4307182&req=5

Fig3: Genetic disposition between PAH patients (blue) and controls (orange) for eachTRPC6SNPs. A: c.1-361; B: c.1-254; C: c.1-218.
Mentions: We found statistically significant differences between patients and controls (p = 0.0077) for TRPC6 c.1-361A > T polymorphism (Figure 2). TT genotype was present in 2 patients (3.7%) but in any control; AT genotype was also more frequent in patients (52%) than controls (31%), whose most common genotype was AA. These results are shown in Figure 3a. Patients showed an allele frequency of 0.690 for A and 0.303 for T, but this frequency was 0.836 for A and 0.163 for T in controls. Patients with this polymorphism were not in Hardy-Weinberg Equilibrium (H-WE) with p = 0.0085 but controls were in H-WE with p = 0.1588. The predominant genotype for IPAH patients was AT (61%) and for APAH patients was AA (50%) (Figure 4a). Comparing the distribution of this polymorphism, in healthy people reached statistically differences with IPAH (p = 0.02), but not with APAH (p = 0.097).Figure 2

Bottom Line: We used a non-parametric test to determine if significant differences were found between the groups studied and chi-square test to compare clinical and hemodynamic variables among genotypes.Several clinical and hemodynamic parameters showed significant differences between carriers and non-carriers of these single nucleotide polymorphisms (SNPs).This study seems to suggest that c.1-361A > T, c.1-254C > G and c.1-218C > T polymorphisms in TRPC6 gene and c.1166A > C polymorphism in AGTR1 could have a role in the development of this disease.

View Article: PubMed Central - PubMed

Affiliation: Department Biochemistry, Genetics and Immunology, Faculty of Biology, University of Vigo, Campus As Lagoas Marcosende S/N, 36310, Vigo, Spain. g.pousada@uvigo.es.

ABSTRACT

Background: Pulmonary arterial hypertension (PAH) is a rare and progressive vascular disorder characterized by increased pulmonary vascular resistance and right heart failure. The aim of this study was to analyze 5'UTR region in canonical transient receptor potential isoform 6 (TRPC6) and 3'UTR region in Angiotensin II type I receptor (AGTR1) genes in patients with idiopathic and associated PAH. Correlation among mutations and clinical and functional parameters was further analyzed.

Methods: Analysis of TRPC6 and AGTR1 genes was performed by polymerase chain reaction (PCR) and direct sequencing. We used a non-parametric test to determine if significant differences were found between the groups studied and chi-square test to compare clinical and hemodynamic variables among genotypes.

Results: Fifty five patients and fifty two controls were included in this study. We found statistically significant differences for c.1-361A > T (p = 0.0077), c.1-254C > G (p < 0.0001) and c.1-218C > T (p = 0.0021) in TRPC6 gene and c.1166A > C (p < 0.001) in AGTR1 gene, between patients and controls. Idiopathic PAH patients (IPAH) and controls presented significant differences for all 3 TRPC6 polymorphisms (p = 0.020), (p = 0.002) and (p = 0.008) respectively, and also showed differences for AGTR1 gene (p < 0.001). In associated PAH (APAH) patients we found statistical differences for c.1-254C > G (p < 0.001) and c.1-218C > T (p = 0.001) in TRPC6 gene and c.1166A > C (p = 0.001) in AGTR1 gene. Several clinical and hemodynamic parameters showed significant differences between carriers and non-carriers of these single nucleotide polymorphisms (SNPs). Nineteen patients were carriers of all 3 SNPs in TRPC6 gene and presented a more severe phenotype with differences in mean pulmonary arterial pressure (p = 0.016), systolic pulmonary arterial pressure (p = 0.040), cardiac index (p < 0.001) and 6 minute walking test (p = 0.049). 16 of these patients harbored the SNP in AGTR1 gene. These patients showed differences in age at diagnosis (p = 0.049), mean pulmonary arterial pressure (p = 0.033), cardiac index (p = 0.002) and 6 minute walking test (p = 0.039).

Conclusions: PAH is a rare disease with pulmonary vascular remodeling caused in part by a heterogeneous constellation of genetic arrangements. This study seems to suggest that c.1-361A > T, c.1-254C > G and c.1-218C > T polymorphisms in TRPC6 gene and c.1166A > C polymorphism in AGTR1 could have a role in the development of this disease.

Show MeSH
Related in: MedlinePlus