Limits...
A novel SNP associated with nighttime pulse pressure in young-onset hypertension patients could be a genetic prognostic factor for cardiovascular events in a general cohort in Taiwan.

Leu HB, Chung CM, Lin SJ, Lu TM, Yang HC, Ho HY, Ting CT, Lin TH, Sheu SH, Tsai WC, Chen JH, Yin WH, Chiu TY, Chen CI, Pan WH, Chen JW - PLoS ONE (2014)

Bottom Line: However, the genetic association of pulse pressure and its clinical impact remain undetermined.We conducted a genome-wide association study of PP using ambulatory BP monitoring in young-onset hypertensive patients and found a significant association between nighttime PP and SNP rs897876 (p = 0.009) at chromosome 2p14, which contains the predicted gene FLJ16124.The T risk allele resulted in a cumulative increase in nighttime PP (β = 1.036 mm Hg, se. = 0.298, p<0.001 per T allele).

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Medicine and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan; Heath Care and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan; Divison of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

ABSTRACT

Background: Pulse pressure (PP) is a risk factor for cardiovascular disease. It has been reported that ambulatory blood pressure (BP) and nighttime BP parameters are heritable traits. However, the genetic association of pulse pressure and its clinical impact remain undetermined.

Method and results: We conducted a genome-wide association study of PP using ambulatory BP monitoring in young-onset hypertensive patients and found a significant association between nighttime PP and SNP rs897876 (p = 0.009) at chromosome 2p14, which contains the predicted gene FLJ16124. Young-onset hypertension patients carrying TT genotypes at rs897876 had higher nighttime PP than those with CT and CC genotypes (TT, 41.6 ± 7.3 mm Hg; CT, 39.1 ± 6.0 mm Hg; CC, 38.9 ± 6.3 mm Hg; p<0.05,). The T risk allele resulted in a cumulative increase in nighttime PP (β = 1.036 mm Hg, se. = 0.298, p<0.001 per T allele). An independent community-based cohort containing 3325 Taiwanese individuals (mean age, 50.2 years) was studied to investigate the genetic impact of rs897876 polymorphisms in determining future cardiovascular events. After an average 7.79 ± 0.28 years of follow-up, the TT genotype of rs897876 was independently associated with an increased risk (in a recessive model) of coronary artery disease (HR, 2.20; 95% CI, 1.20-4.03; p = 0.01) and total cardiovascular events (HR, 1.99; 95% CI, 1.29-3.06; p = 0.002), suggesting that the TT genotype of rs897876C, which is associated with nighttime pulse pressure in young-onset hypertension patients, could be a genetic prognostic factor of cardiovascular events in the general cohort.

Conclusion: The TT genotype of rs897876C at 2p14 identified in young-onset hypertensive had higher nighttime PP and could be a genetic prognostic factor of cardiovascular events in the general cohort in Taiwan.

Show MeSH

Related in: MedlinePlus

Kaplan-Meier estimates of survival-free cardiovascular events including stroke (A), acute coronary syndrome (B), cardiovascular death (C) and total cardiovascular events (D) according to rs897876 genotypes in a cohort study.The event-free survival rates for acute coronary syndrome and total cardiovascular events were significantly different in TT vs. CC+CT genotypes (log-rank test, p = 0.0031 and p = 0.009, respectively).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4043733&req=5

pone-0097919-g003: Kaplan-Meier estimates of survival-free cardiovascular events including stroke (A), acute coronary syndrome (B), cardiovascular death (C) and total cardiovascular events (D) according to rs897876 genotypes in a cohort study.The event-free survival rates for acute coronary syndrome and total cardiovascular events were significantly different in TT vs. CC+CT genotypes (log-rank test, p = 0.0031 and p = 0.009, respectively).

Mentions: To determine the clinical significance of the nighttime PP-associated SNP found among young-onset hypertensive, genotyping for rs897876 was performed in a prospective cohort study, the CVDFACTS study, to evaluate the association of future cardiovascular events with rs897876. The genotype call rate was above 99.4%. The CVDFACTS study enrolled a total of 3325 subjects, 1513 males and 1812 females, with a mean age of 50.2±12.3. The CVDFACTS cohort used in this study consisted of a total of 389 hypertensive patients, 204 (52%) of whom were young-onset hypertensive patients. The young onset hypertensive subjects have higher diastolic blood pressure and higher BMI. Subject with hypertension diagnosed after age 50 have higher fasting glucose, and higher triglyceride values (Table S2). After an average of 7.8 years of follow-up, 68 ischemic stroke events, 99 acute coronary syndrome events, 34 cardiovascular-related deaths and 190 total events were identified (Table 4). In this independent cohort, the T allele of rs897876 was significantly associated with CAD and total cardiovascular (CV) events (under a recessive model for the variant allele, log-rank p for CAD = 0.031 and for total CV events = 0.009) (Table 5). Figure 3 shows the effect of rs897876 polymorphisms on clinical outcomes in the cohort participants. The TT genotype of rs897876 was associated significantly with a higher risk of developing CAD and total cardiovascular events. After adjusting for comorbidity, including history of diabetes mellitus, smoking habit, gender, hypertension, waist circumference, total cholesterol, BMI, and age, the TT genotype of rs897876 still independently associated with CAD (hazard ratio, 2.20; 95% CI, 1.20–4.03; p = 0.01) and total CV events (hazard ratio, 1.99; 95% CI, 1.29–3.06; p = 0.002) (Table 6), indicating that the TT genotype of rs897876C genotypes, which was identified based on the ambulatory night PP values of young-onset hypertension patients, was associated with a higher risk of future cardiovascular events.


A novel SNP associated with nighttime pulse pressure in young-onset hypertension patients could be a genetic prognostic factor for cardiovascular events in a general cohort in Taiwan.

Leu HB, Chung CM, Lin SJ, Lu TM, Yang HC, Ho HY, Ting CT, Lin TH, Sheu SH, Tsai WC, Chen JH, Yin WH, Chiu TY, Chen CI, Pan WH, Chen JW - PLoS ONE (2014)

Kaplan-Meier estimates of survival-free cardiovascular events including stroke (A), acute coronary syndrome (B), cardiovascular death (C) and total cardiovascular events (D) according to rs897876 genotypes in a cohort study.The event-free survival rates for acute coronary syndrome and total cardiovascular events were significantly different in TT vs. CC+CT genotypes (log-rank test, p = 0.0031 and p = 0.009, respectively).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043733&req=5

pone-0097919-g003: Kaplan-Meier estimates of survival-free cardiovascular events including stroke (A), acute coronary syndrome (B), cardiovascular death (C) and total cardiovascular events (D) according to rs897876 genotypes in a cohort study.The event-free survival rates for acute coronary syndrome and total cardiovascular events were significantly different in TT vs. CC+CT genotypes (log-rank test, p = 0.0031 and p = 0.009, respectively).
Mentions: To determine the clinical significance of the nighttime PP-associated SNP found among young-onset hypertensive, genotyping for rs897876 was performed in a prospective cohort study, the CVDFACTS study, to evaluate the association of future cardiovascular events with rs897876. The genotype call rate was above 99.4%. The CVDFACTS study enrolled a total of 3325 subjects, 1513 males and 1812 females, with a mean age of 50.2±12.3. The CVDFACTS cohort used in this study consisted of a total of 389 hypertensive patients, 204 (52%) of whom were young-onset hypertensive patients. The young onset hypertensive subjects have higher diastolic blood pressure and higher BMI. Subject with hypertension diagnosed after age 50 have higher fasting glucose, and higher triglyceride values (Table S2). After an average of 7.8 years of follow-up, 68 ischemic stroke events, 99 acute coronary syndrome events, 34 cardiovascular-related deaths and 190 total events were identified (Table 4). In this independent cohort, the T allele of rs897876 was significantly associated with CAD and total cardiovascular (CV) events (under a recessive model for the variant allele, log-rank p for CAD = 0.031 and for total CV events = 0.009) (Table 5). Figure 3 shows the effect of rs897876 polymorphisms on clinical outcomes in the cohort participants. The TT genotype of rs897876 was associated significantly with a higher risk of developing CAD and total cardiovascular events. After adjusting for comorbidity, including history of diabetes mellitus, smoking habit, gender, hypertension, waist circumference, total cholesterol, BMI, and age, the TT genotype of rs897876 still independently associated with CAD (hazard ratio, 2.20; 95% CI, 1.20–4.03; p = 0.01) and total CV events (hazard ratio, 1.99; 95% CI, 1.29–3.06; p = 0.002) (Table 6), indicating that the TT genotype of rs897876C genotypes, which was identified based on the ambulatory night PP values of young-onset hypertension patients, was associated with a higher risk of future cardiovascular events.

Bottom Line: However, the genetic association of pulse pressure and its clinical impact remain undetermined.We conducted a genome-wide association study of PP using ambulatory BP monitoring in young-onset hypertensive patients and found a significant association between nighttime PP and SNP rs897876 (p = 0.009) at chromosome 2p14, which contains the predicted gene FLJ16124.The T risk allele resulted in a cumulative increase in nighttime PP (β = 1.036 mm Hg, se. = 0.298, p<0.001 per T allele).

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Medicine and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan; Heath Care and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan; Divison of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

ABSTRACT

Background: Pulse pressure (PP) is a risk factor for cardiovascular disease. It has been reported that ambulatory blood pressure (BP) and nighttime BP parameters are heritable traits. However, the genetic association of pulse pressure and its clinical impact remain undetermined.

Method and results: We conducted a genome-wide association study of PP using ambulatory BP monitoring in young-onset hypertensive patients and found a significant association between nighttime PP and SNP rs897876 (p = 0.009) at chromosome 2p14, which contains the predicted gene FLJ16124. Young-onset hypertension patients carrying TT genotypes at rs897876 had higher nighttime PP than those with CT and CC genotypes (TT, 41.6 ± 7.3 mm Hg; CT, 39.1 ± 6.0 mm Hg; CC, 38.9 ± 6.3 mm Hg; p<0.05,). The T risk allele resulted in a cumulative increase in nighttime PP (β = 1.036 mm Hg, se. = 0.298, p<0.001 per T allele). An independent community-based cohort containing 3325 Taiwanese individuals (mean age, 50.2 years) was studied to investigate the genetic impact of rs897876 polymorphisms in determining future cardiovascular events. After an average 7.79 ± 0.28 years of follow-up, the TT genotype of rs897876 was independently associated with an increased risk (in a recessive model) of coronary artery disease (HR, 2.20; 95% CI, 1.20-4.03; p = 0.01) and total cardiovascular events (HR, 1.99; 95% CI, 1.29-3.06; p = 0.002), suggesting that the TT genotype of rs897876C, which is associated with nighttime pulse pressure in young-onset hypertension patients, could be a genetic prognostic factor of cardiovascular events in the general cohort.

Conclusion: The TT genotype of rs897876C at 2p14 identified in young-onset hypertensive had higher nighttime PP and could be a genetic prognostic factor of cardiovascular events in the general cohort in Taiwan.

Show MeSH
Related in: MedlinePlus