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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.

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Signal-intensity plots showing the genome-wide associations of single-nucleotide polymorphisms (SNPs) with daytime PP (1A) and nighttime PP (1B) in young-onset hypertensives.
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pone-0097919-g001: Signal-intensity plots showing the genome-wide associations of single-nucleotide polymorphisms (SNPs) with daytime PP (1A) and nighttime PP (1B) in young-onset hypertensives.

Mentions: Table 1 shows the baseline characteristics of young-onset hypertension patients in the discovery GWAS and the subsequent replication study. The p-values from the discovery GWAS for association tests of daytime PP and nighttime PP are shown in Figure 1. The top scoring SNPs for association with ambulatory PP parameters are shown in Table 2. The SNP with the lowest p-value (2.72×10−7) for the trait of nighttime PP was rs6696698, located on chromosome 1 (Figure 1A). The EIGENSTRAT utility of the EIGENSOFT package version 2.0 [24] was used to quantify and correct for population sub-structure and adjust for population stratification in association analyses. There was no evidence of population stratification in the hypertensive subjects (Table S1). Multidimensional scaling analysis using PLINK also showed similar results (Fig. S1). In the GWAS analysis no SNP exceeded the GWAS significance threshold for either of the ABP-monitoring phenotypes (daytime or nighttime PP). For each trait, considering that some SNP markers in the same area were in moderate linkage disequilibrium, all SNP markers achieving a –log p value more than 5 with a minor allele frequency more than 5% were selected in the replication study (Table 2). Only one SNP marker, rs897876, which is in the predicted gene FLJ12164 at 2p14, was significantly associated with nighttime PP (p = 0.009) in the replication study (Table 2, Figure2). Table 3 showed the baseline characteristics of these young-onset hypertension subjects according to genotypes of rs897876. Subjects with the TT genotype at rs897876 had higher nighttime PP values than those with the CT or CC genotype (TT, 41.6±7.3 mm Hg; CT, 39.1±6. 3 mm Hg; CC, 38.9±6.3 mm Hg; p<0.05). After regression analysis adjusting for age, gender, BMI, and hypertension treatment regimens, the T allele of rs897876 was additively associated with increased nighttime PP (β = 1.036 mm Hg, se. = 0.298, p<0.001 per T allele).


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)

Signal-intensity plots showing the genome-wide associations of single-nucleotide polymorphisms (SNPs) with daytime PP (1A) and nighttime PP (1B) in young-onset hypertensives.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0097919-g001: Signal-intensity plots showing the genome-wide associations of single-nucleotide polymorphisms (SNPs) with daytime PP (1A) and nighttime PP (1B) in young-onset hypertensives.
Mentions: Table 1 shows the baseline characteristics of young-onset hypertension patients in the discovery GWAS and the subsequent replication study. The p-values from the discovery GWAS for association tests of daytime PP and nighttime PP are shown in Figure 1. The top scoring SNPs for association with ambulatory PP parameters are shown in Table 2. The SNP with the lowest p-value (2.72×10−7) for the trait of nighttime PP was rs6696698, located on chromosome 1 (Figure 1A). The EIGENSTRAT utility of the EIGENSOFT package version 2.0 [24] was used to quantify and correct for population sub-structure and adjust for population stratification in association analyses. There was no evidence of population stratification in the hypertensive subjects (Table S1). Multidimensional scaling analysis using PLINK also showed similar results (Fig. S1). In the GWAS analysis no SNP exceeded the GWAS significance threshold for either of the ABP-monitoring phenotypes (daytime or nighttime PP). For each trait, considering that some SNP markers in the same area were in moderate linkage disequilibrium, all SNP markers achieving a –log p value more than 5 with a minor allele frequency more than 5% were selected in the replication study (Table 2). Only one SNP marker, rs897876, which is in the predicted gene FLJ12164 at 2p14, was significantly associated with nighttime PP (p = 0.009) in the replication study (Table 2, Figure2). Table 3 showed the baseline characteristics of these young-onset hypertension subjects according to genotypes of rs897876. Subjects with the TT genotype at rs897876 had higher nighttime PP values than those with the CT or CC genotype (TT, 41.6±7.3 mm Hg; CT, 39.1±6. 3 mm Hg; CC, 38.9±6.3 mm Hg; p<0.05). After regression analysis adjusting for age, gender, BMI, and hypertension treatment regimens, the T allele of rs897876 was additively associated with increased nighttime PP (β = 1.036 mm Hg, se. = 0.298, p<0.001 per T allele).

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