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  • Ovid Technologies (Wolters Kluwer Health)  (4)
  • Ji, Xu  (4)
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  • Ovid Technologies (Wolters Kluwer Health)  (4)
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  • 1
    Online Resource
    Online Resource
    Genome-Wide Association Study Identifies 8 Novel Loci Associated With Blood Pressure Responses to Interventions in Han Chinese
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Circulation: Cardiovascular Genetics Vol. 6, No. 6 ( 2013-12), p. 598-607
    Details
    In: Circulation: Cardiovascular Genetics, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 6 ( 2013-12), p. 598-607
    Abstract: Blood pressure (BP) responses to dietary sodium and potassium intervention and cold pressor test vary considerably among individuals. We aimed to identify novel genetic variants influencing individuals’ BP responses to dietary intervention and cold pressor test. Methods and Results— We conducted a genome-wide association study of BP responses in 1881 Han Chinese and de novo genotyped top findings in 698 Han Chinese. Diet-feeding study included a 7-day low-sodium (51.3 mmol/d), a 7-day high-sodium (307.8 mmol/d), and a 7-day high-sodium plus potassium supplementation (60 mmol/d). Nine BP measurements were obtained during baseline observation and each intervention period. The meta-analyses identified 8 novel loci for BP phenotypes, which physically mapped in or near PRMT6 ( P =7.29×10 –9 ), CDCA7 ( P =3.57×10 –8 ), PIBF1 ( P =1.78×10 –9 ), ARL4C ( P =1.86×10 –8 ), IRAK1BP1 ( P =1.44×10 −10 ), SALL1 ( P =7.01×10 –13 ), TRPM8 ( P =2.68×10 –8 ), and FBXL13 ( P =3.74×10 –9 ). There was a strong dose–response relationship between the number of risk alleles of these independent single-nucleotide polymorphisms and the risk of developing hypertension during the 7.5-year follow-up in the study participants. Compared with those in the lowest quartile of risk alleles, odds ratios (95% confidence intervals) for those in the second, third, and fourth quartiles were 1.39 (0.97, 1.99), 1.72 (1.19, 2.47), and 1.84 (1.29, 2.62), respectively ( P =0.0003 for trend). Conclusions— Our study identified 8 novel loci for BP responses to dietary sodium and potassium intervention and cold pressor test. The effect size of these novel loci on BP phenotypes is much larger than those reported by the previously published studies. Furthermore, these variants predict the risk of developing hypertension among individuals with normal BP at baseline.
    Type of Medium: Online Resource
    ISSN: 1942-325X , 1942-3268
    URL: Article
    DOI: 10.1161/CIRCGENETICS.113.000307
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 2927603-2
    detail.hit.zdb_id: 2457085-0
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Genetic Susceptibility to Lipid Levels and Lipid Change Over Time and Risk of Incident Hyperlipidemia in Chinese Populations
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Circulation: Cardiovascular Genetics Vol. 9, No. 1 ( 2016-02), p. 37-44
    Details
    In: Circulation: Cardiovascular Genetics, Ovid Technologies (Wolters Kluwer Health), Vol. 9, No. 1 ( 2016-02), p. 37-44
    Abstract: Multiple genetic loci associated with lipid levels have been identified predominantly in Europeans, and the issue of to what extent these genetic loci can predict blood lipid levels increases over time and the incidence of future hyperlipidemia remains largely unknown. Methods and Results— We conducted a meta-analysis of genome-wide association studies of lipid levels in 8344 subjects followed by replication studies including 14 739 additional individuals. We replicated 17 previously reported loci. We also newly identified 3 Chinese-specific variants in previous regions ( HLA-C , LIPG , and LDLR ) with genome-wide significance. Almost all the variants contributed to lipid levels change and incident hyperlipidemia 〉 8.1-year follow-up among 6428 individuals of a prospective cohort study. The strongest associations for lipid levels change were detected at LPL , TRIB1 , APOA1-C3-A4-A5 , LIPC , CETP , and LDLR ( P range from 4.84×10 −4 to 4.62×10 −18 ), whereas LPL , TRIB1 , ABCA1 , APOA1-C3-A4-A5 , CETP , and APOE displayed significant strongest associations for incident hyperlipidemia ( P range from 1.20×10 −3 to 4.67×10 −16 ). The 4 lipids genetic risk scores were independently associated with linear increases in their corresponding lipid levels and risk of incident hyperlipidemia. A C -statistics analysis showed significant improvement in the prediction of incident hyperlipidemia on top of traditional risk factors including the baseline lipid levels. Conclusions— These findings identified some evidence for allelic heterogeneity in Chinese when compared with Europeans in relation to lipid associations. The individual variants and those cumulative effects were independent risk factors for lipids increase and incident hyperlipidemia.
    Type of Medium: Online Resource
    ISSN: 1942-325X , 1942-3268
    URL: Article
    DOI: 10.1161/CIRCGENETICS.115.001096
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2927603-2
    detail.hit.zdb_id: 2457085-0
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  • 3
    Online Resource
    Online Resource
    Genetic Predisposition to Higher Blood Pressure Increases Risk of Incident Hypertension and Cardiovascular Diseases in Chinese
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Hypertension Vol. 66, No. 4 ( 2015-10), p. 786-792
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 66, No. 4 ( 2015-10), p. 786-792
    Abstract: Although multiple genetic markers associated with blood pressure have been identified by genome-wide association studies, their aggregate effect on risk of incident hypertension and cardiovascular disease is uncertain, particularly among East Asian who may have different genetic and environmental exposures from Europeans. We aimed to examine the association between genetic predisposition to higher blood pressure and risk of incident hypertension and cardiovascular disease in 26 262 individuals in 2 Chinese population-based prospective cohorts. A genetic risk score was calculated based on 22 established variants for blood pressure in East Asian. We found the genetic risk score was significantly and independently associated with linear increases in blood pressure and risk of incident hypertension and cardiovascular disease ( P range from 4.57×10 –3 to 3.10×10 –6 ). In analyses adjusted for traditional risk factors including blood pressure, individuals carrying most blood pressure–related risk alleles (top quintile of genetic score distribution) had 40% (95% confidence interval, 18–66) and 26% (6–45) increased risk for incident hypertension and cardiovascular disease, respectively, when compared with individuals in the bottom quintile. The genetic risk score also significantly improved discrimination for incident hypertension and cardiovascular disease and led to modest improvements in risk reclassification for cardiovascular disease (all the P 〈 0.05). Our data indicate that genetic predisposition to higher blood pressure is an independent risk factor for blood pressure increase and incident hypertension and cardiovascular disease and provides modest incremental information to cardiovascular disease risk prediction. The potential clinical use of this panel of blood pressure–associated polymorphisms remains to be determined.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.115.05961
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 2094210-2
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  • 4
    Online Resource
    Online Resource
    Abstract P234: Genetic Variants of the Kallikrein-kinin System Associated with the Salt Sensitivity of Blood Pressure: The GenSalt Study
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Circulation Vol. 125, No. suppl_10 ( 2012-03-13)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 125, No. suppl_10 ( 2012-03-13)
    Abstract: The kallikrein-kinin system (KKS) has been implicated in the pathogenesis of salt-sensitive hypertension in animal models. We comprehensively examined the association between genetic variants of the KKS and blood pressure (BP) response to dietary sodium intervention among participants of the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study. A 7-day low-sodium dietary intervention followed by a 7-day high-sodium dietary intervention was carried out among 1,906 GenSalt participants from rural areas of north China. Nine BP measurements were obtained at baseline and on the last three days of each intervention period using a random-zero sphygmomanometer. The percentage changes in mean BP from baseline to low-sodium intervention and from low-sodium to high-sodium intervention were used to assess individual salt-sensitivity. A total of 205 tagSNPs and functional SNPs of eleven genes of the KKS ( BDKRB1 , BDKRB2 , CPN1 , CPN2 , CPM , ECE1 , KLK1 , KLKB1 , KNG1 , MME , SERPINA4 ) were selected and genotyped in this study. Single marker analyses were conducted using the Family Based Association Test program. Genetic variants in the bradykinin receptor B2 ( BDKRB2 ) and endothelin converting enzyme 1 ( ECE1 ) genes showed significant associations with salt sensitivity even after adjusting for multiple testing using the false discovery rate method. SNP rs11847625 of BDKRB2 was significantly associated with systolic BP (SBP) response to low-sodium intervention ( P = 0.0001). Compared to its major allele G, carriers of the minor allele C had greater SBP decrease during low-sodium intervention. Furthermore, a haplotype containing allele C was associated with greater SBP increase to high-sodium intervention ( P = 0.0009). Seven SNPs of ECE1 , one of the degrading enzymes of kinins, were significantly associated with diastolic BP (DBP) response to low-sodium intervention ( P values ranged from 0.0003 to 0.002). Two haplotypes in the linkage disequilibrium block including these seven SNPs were significantly associated with DBP response to low-sodium intervention (P=0.0004 and 0.003, respectively). Our study found that the genetic variants of the KKS were associated with salt sensitivity of BP. Replication and functional studies of the identified variants are warranted in the future.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.125.suppl_10.AP234
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 1466401-X
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