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CYP17A1 and Blood Pressure Reactivity to Stress in Adolescence.

Van Woudenberg M, Shin J, Bernard M, Syme C, Abrahamowicz M, Leonard G, Perron M, Richer L, Veillette S, Gaudet D, Paus T, Pausova Z - Int J Hypertens (2015)

Bottom Line: Our results showed that the variant of CYP17A1 rs10786718 was associated with enhanced BP reactivity to the mental but not physical challenge and in males but not females.Resting BP was not associated with the CYP17A1 variant in either sex.These results suggest that, in adolescent males but not females, CYP17A1 enhances BP reactivity to mental stress.

View Article: PubMed Central - PubMed

Affiliation: The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada M5G 1X8.

ABSTRACT
Adolescents who exhibit exaggerated blood pressure (BP) reactivity to physical and mental challenges are at increased risk of developing hypertension in adulthood. BP at rest and in response to challenges is higher in males than females, beginning in early adolescence. CYP17A1 is one of the well-established gene loci of adult hypertension. Here, we investigated whether this gene locus is associated with elevated BP at rest and in response to physical (active standing) and mental (math stress) challenges in adolescence. We studied 496 male and 532 female adolescents (age 12-18 years) who were recruited from a genetic founder population. Our results showed that the variant of CYP17A1 rs10786718 was associated with enhanced BP reactivity to the mental but not physical challenge and in males but not females. In males, BP increase in response to math stress was higher in major versus minor allele homozygotes by 7.6 mm Hg (P = 8.3 × 10(-6)). Resting BP was not associated with the CYP17A1 variant in either sex. These results suggest that, in adolescent males but not females, CYP17A1 enhances BP reactivity to mental stress. Whether this effect contributes to the higher prevalence of hypertension in males than females later in life remains to be determined.

No MeSH data available.


Related in: MedlinePlus

CYP17A1 locus and SBP in response to physical and mental challenges and at rest. Individual points indicate −log10 (P values) for associations of SNPs within the CYP17A1 locus and studied SBP phenotypes. Plots on the left and right show the results in males and females, respectively. Data were adjusted for age, height, and, when appropriate (SBP reactivity to standing and mental stress), initial SBP. The SNP, rs10786718, demonstrating the strongest association with SBP reactivity to math stress in males is indicated in purple and is the index SNP in all plots. The correlation (r2) between this index SNP, rs10786718, and each of the other tested SNPs in the region is shown in red (1 ≥ r2 ≥ 0.8), orange (0.8 > r2 ≥ 0.6), green (0.6 > r2 ≥ 0.4), light blue (0.4 > r2 ≥ 0.2), or dark blue (0.2 > r2 ≥ 0) colors. Gene positions are indicated at the bottom. The LD was calculated based on the 1,000 Genomes Project (EUR reference panel, March 2012 version); the chromosome positions are based on human genome hg19.
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Related In: Results  -  Collection


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fig3: CYP17A1 locus and SBP in response to physical and mental challenges and at rest. Individual points indicate −log10 (P values) for associations of SNPs within the CYP17A1 locus and studied SBP phenotypes. Plots on the left and right show the results in males and females, respectively. Data were adjusted for age, height, and, when appropriate (SBP reactivity to standing and mental stress), initial SBP. The SNP, rs10786718, demonstrating the strongest association with SBP reactivity to math stress in males is indicated in purple and is the index SNP in all plots. The correlation (r2) between this index SNP, rs10786718, and each of the other tested SNPs in the region is shown in red (1 ≥ r2 ≥ 0.8), orange (0.8 > r2 ≥ 0.6), green (0.6 > r2 ≥ 0.4), light blue (0.4 > r2 ≥ 0.2), or dark blue (0.2 > r2 ≥ 0) colors. Gene positions are indicated at the bottom. The LD was calculated based on the 1,000 Genomes Project (EUR reference panel, March 2012 version); the chromosome positions are based on human genome hg19.

Mentions: Genotype imputation was used to equate the set of SNPs of the adolescents genotyped on each platform and to increase the SNP density. Haplotype phasing was performed with SHAPEIT [33] using an overlapping subset of 313,653 post-quality-control SNPs that were present on both genotyping platforms and the 1,000 Genomes SNPs in European reference panel (Phase 1, Release 3). Imputation was conducted on the phased data with IMPUTE2 [34]. Markers with low imputation quality (information score < 0.5) or low minor allele frequency (<0.01) were removed. After this imputation quality control, a total of 1,392 typed and imputed SNPs were available for a segment of human chromosome 10 that covered the entire previously reported CYP17A1 locus of adult SBP, DBP, and hypertension (~400 kb from CYP17A1 to NT5C2 [17]) and its flanking sequences (90 kb upstream of CYP17A1 and 147 kb downstream of NT5C2, Figure 3 and Figure S4; see Supplementary Material available online at http://dx.doi.org/10.1155/2015/734586).


CYP17A1 and Blood Pressure Reactivity to Stress in Adolescence.

Van Woudenberg M, Shin J, Bernard M, Syme C, Abrahamowicz M, Leonard G, Perron M, Richer L, Veillette S, Gaudet D, Paus T, Pausova Z - Int J Hypertens (2015)

CYP17A1 locus and SBP in response to physical and mental challenges and at rest. Individual points indicate −log10 (P values) for associations of SNPs within the CYP17A1 locus and studied SBP phenotypes. Plots on the left and right show the results in males and females, respectively. Data were adjusted for age, height, and, when appropriate (SBP reactivity to standing and mental stress), initial SBP. The SNP, rs10786718, demonstrating the strongest association with SBP reactivity to math stress in males is indicated in purple and is the index SNP in all plots. The correlation (r2) between this index SNP, rs10786718, and each of the other tested SNPs in the region is shown in red (1 ≥ r2 ≥ 0.8), orange (0.8 > r2 ≥ 0.6), green (0.6 > r2 ≥ 0.4), light blue (0.4 > r2 ≥ 0.2), or dark blue (0.2 > r2 ≥ 0) colors. Gene positions are indicated at the bottom. The LD was calculated based on the 1,000 Genomes Project (EUR reference panel, March 2012 version); the chromosome positions are based on human genome hg19.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4321855&req=5

fig3: CYP17A1 locus and SBP in response to physical and mental challenges and at rest. Individual points indicate −log10 (P values) for associations of SNPs within the CYP17A1 locus and studied SBP phenotypes. Plots on the left and right show the results in males and females, respectively. Data were adjusted for age, height, and, when appropriate (SBP reactivity to standing and mental stress), initial SBP. The SNP, rs10786718, demonstrating the strongest association with SBP reactivity to math stress in males is indicated in purple and is the index SNP in all plots. The correlation (r2) between this index SNP, rs10786718, and each of the other tested SNPs in the region is shown in red (1 ≥ r2 ≥ 0.8), orange (0.8 > r2 ≥ 0.6), green (0.6 > r2 ≥ 0.4), light blue (0.4 > r2 ≥ 0.2), or dark blue (0.2 > r2 ≥ 0) colors. Gene positions are indicated at the bottom. The LD was calculated based on the 1,000 Genomes Project (EUR reference panel, March 2012 version); the chromosome positions are based on human genome hg19.
Mentions: Genotype imputation was used to equate the set of SNPs of the adolescents genotyped on each platform and to increase the SNP density. Haplotype phasing was performed with SHAPEIT [33] using an overlapping subset of 313,653 post-quality-control SNPs that were present on both genotyping platforms and the 1,000 Genomes SNPs in European reference panel (Phase 1, Release 3). Imputation was conducted on the phased data with IMPUTE2 [34]. Markers with low imputation quality (information score < 0.5) or low minor allele frequency (<0.01) were removed. After this imputation quality control, a total of 1,392 typed and imputed SNPs were available for a segment of human chromosome 10 that covered the entire previously reported CYP17A1 locus of adult SBP, DBP, and hypertension (~400 kb from CYP17A1 to NT5C2 [17]) and its flanking sequences (90 kb upstream of CYP17A1 and 147 kb downstream of NT5C2, Figure 3 and Figure S4; see Supplementary Material available online at http://dx.doi.org/10.1155/2015/734586).

Bottom Line: Our results showed that the variant of CYP17A1 rs10786718 was associated with enhanced BP reactivity to the mental but not physical challenge and in males but not females.Resting BP was not associated with the CYP17A1 variant in either sex.These results suggest that, in adolescent males but not females, CYP17A1 enhances BP reactivity to mental stress.

View Article: PubMed Central - PubMed

Affiliation: The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada M5G 1X8.

ABSTRACT
Adolescents who exhibit exaggerated blood pressure (BP) reactivity to physical and mental challenges are at increased risk of developing hypertension in adulthood. BP at rest and in response to challenges is higher in males than females, beginning in early adolescence. CYP17A1 is one of the well-established gene loci of adult hypertension. Here, we investigated whether this gene locus is associated with elevated BP at rest and in response to physical (active standing) and mental (math stress) challenges in adolescence. We studied 496 male and 532 female adolescents (age 12-18 years) who were recruited from a genetic founder population. Our results showed that the variant of CYP17A1 rs10786718 was associated with enhanced BP reactivity to the mental but not physical challenge and in males but not females. In males, BP increase in response to math stress was higher in major versus minor allele homozygotes by 7.6 mm Hg (P = 8.3 × 10(-6)). Resting BP was not associated with the CYP17A1 variant in either sex. These results suggest that, in adolescent males but not females, CYP17A1 enhances BP reactivity to mental stress. Whether this effect contributes to the higher prevalence of hypertension in males than females later in life remains to be determined.

No MeSH data available.


Related in: MedlinePlus