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The association study of single nucleotide polymorphisms and haplotypes of TERT gene with longevity in Xinjiang Uygur population
Abstracts
Klotho gene at rs9536314 was correlated with renal function decline among long-lived Uygur. doi:10.1016/j.ijcard.2011.08.736 0162 The association study of single nucleotide polymorphisms and haplotypes of TERT gene with longevity in Xinjiang Uygur population XINJUAN XU, XIAOHUI LIANG, YULAN CHEN, ZHULEPIYA SIMAYI, SUHUA LI Department of Hypertension, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China Objective: We investigated the association of single nucleotide polymorphisms and haplotypes of TERT gene with longevity in Xinjiang Uygur population. Methods: A total of 361 Uygur subjects were selected including 112 individuals ≥90 years old and 249 controls. The tagging single nucleotide polymorphisms (tSNPs) were selected. The locus of telomerase reverse transcriptase (TERT) gene including rs2736098 (SNP1), rs2736100(SNP2), rs2853676(SNP3), rs10069690(SNP4), rs4975605 (SNP5), rs2075786(SNP6), rs2736118(SNP7), rs2853691 (SNP8) were genotyped by snapshot method and the haplotype distribution was estimated. Results: (1) The distributions of TTgenotype and T allele of SNP2 (SNP rs2736100) in longevity group were lower than in control group and P equals to 0.026, 0.009. The SNP rs2736100 was significantly associated with longevity (TT versus GG: P = 0.008, OR = 0.392, 95%CI: 0.193 ~ 0.796; GT + TT versus GG: P = 0.023, OR= 0.574, 95%CI: 0.355~ 0.928; T versus G: P = 0.009, OR= 0.652, 95%CI: 0.473 ~ 0.900). (2) The distributions of CC genotype and C allele of SNP6 (SNP rs2075786) in longevity group were lower than in control group and P equals to 0.044, 0.009. The SNP rs2075786 was significantly associated with longevity (CC versus TT: P = 0.013, OR = 0.426, 95%CI: 0.216 ~ 0.842; C versus T: P = 0.009, OR = 0.647, 95%CI: 0.465 ~ 0.899). (3) There was no statistically significant difference in the haplotype analysis. (4) Pulse pressure (PP) and pulse pressure index (PPI) in GT + TT genotype combination were markedly higher than in GG genotype of TERT SNP2 in longevity group, while PPI in TC + CC genotype was markedly higher than in TT genotype of TERT SNP6 in control group. Conclusion: Our study revealed that TERT gene rs2736100 and rs2075786 polymorphisms might be associated with longevity in Xinjiang Uygur population. TT genotype, T allele of rs2736100 and CC genotype, C allele of rs2075786 were the adverse factors of longevity. rs2736100 and rs2075786 might be associated with longevity through impacts on vascular function. doi:10.1016/j.ijcard.2011.08.737 0163 The association study of single nucleotide polymorphisms and haplotypes of VEGF gene with longevity in Xinjiang Uygur population XINJUAN XU, XIAOHUI LIANG, YULAN CHEN, ZHULEPIYA SIMAYI, SUHUA LI Department of Hypertension, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China Objective: We investigated the association of single nucleotide polymorphisms and haplotypes of VEGF gene with longevity in Xinjiang Uygur population. Methods: A case-control design was applied in this study. In brief, a total of 361 Uygur subjects were selected in the study including 112 individuals ≥90 years old and
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249 controls. The tagging single nucleotide polymorphisms (tSNPs) were selected. The locus of vascular endothelial growth factor (VEGF) gene including rs2146323 (SNP1), rs3024997 (SNP2), rs10434 (SNP3) were genotyped by snapshot method and the haplotype distribution was estimated. Results: (1) Three common SNPs of VEGF gene were chosen to be tagging SNPs. All polymorphisms were in Hardy-Weinberg equilibrium both in longevity and in control group. The frequencies of C and A allele of VEGF SNP1 in longevity group were 70.1%, 29.9% and 62.3%, 37.7% in the control group. The frequencies of SNP1 genotypes of CC, CA and AA in longevity group were 47.3%, 45.5%, 7.2% and 42.6%, 39.3%, 18.1% in control group, respectively. The distributions of AA genotype and A allele of SNP1 (SNP rs2146323) in longevity group were lower than in control group and P equals to 0.025, 0.041. The SNP rs2146323 was significantly associated with longevity (AA versus CC: P = 0.011, OR = 0.356, 95%CI: 0.156~ 0.808; A versus C: P = 0.041, OR = 0.704, 95%CI: 0.502 ~ 0.987). (2) The haplotype analysis revealed that the frequency of Hap1-CG was highest in both groups. The frequency of Hap1-CG was higher in longevity group than in control group, while the frequencies of Hap2-CA, Hap3-AG were lower in longevity group. There was no statistically significant difference. (3) The level of pulse pressure (PP) in CA + AA genotype combination was markedly higher than in CC genotype of VEGF SNP1 in control group. Conclusion: VEGF gene rs2146323 polymorphism might be associated with longevity. AA genotype and A allele were the adverse factors of longevity in Xinjiang Uygur population. rs2146323 might be associated with longevity through impacts on vascular function. doi:10.1016/j.ijcard.2011.08.738 0175 The neuropeptide catestatin promotes vascular smooth muscle cell proliferation through the Ca2+-calcineurin-NFAT signaling pathway XIAOXIA GUO, NINGLING SUN Department of Cardiology, People's Hospital, Peking University, Beijing, China Objective: We investigated the proliferative effect of catestatin (CST) on vascular smooth muscle cells (VSMCs) and furthermore researched its molecular mechanism. Methods: VSMCs were growth-arrested by incubating in DMEM containing 0.1% normal calf serum for 24 h. Growth-arrested cells were incubated for 24 h with concentrations of CST ranging from 10− 10–10− 6 mol/L. In additional experiments, growth-arrested VSMCs were treated with CST (1 μM) for 24 h (CST group), or incubated for 1 h with 1 μM cyclosporin A (CsA) prior to CST treatment (CST + CsA group). Cells treated with DMEM containing 0.1% normal calf serum or CsA alone were used as the control group or CsA group. Cell proliferation was assayed using Cell Counting kit-8 and cell cycle analysis was performed by flow cytometry. Intracellular calcium ion concentration ([Ca2+]i) was monitored by confocal microscope, and the expression of proliferative genes were measured by real-time RTPCR. Coimmunoprecipitation assay was carried for showing the interaction between calmodulin and calcineurin. Immunofluorescence experiments and western blots were performed for determining the intracellular localization of NFATc1. Results: Catestatin caused a dose-dependent induction of proliferation in VSMCs, exerting its maximal effect at 1 μM. In quiescent VSMCs, CST induced an increase in [Ca2+]i characterized by an initial Ca2+ spike followed by a sustained elevated plateau phase. The calcineurin inhibitor CsA decreases VSMC growth and proliferative gene expression induced by CST. CST favored the formation of calmodulin/calcineurin complexes and promoted translocation of NFATc1 from the cytoplasm to the nucleus, reflecting increased
Klotho gene at rs9536314 was correlated with renal function decline among long-lived Uygur. doi:10.1016/j.ijcard.2011.08.736 0162 The association study of single nucleotide polymorphisms and haplotypes of TERT gene with longevity in Xinjiang Uygur population XINJUAN XU, XIAOHUI LIANG, YULAN CHEN, ZHULEPIYA SIMAYI, SUHUA LI Department of Hypertension, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China Objective: We investigated the association of single nucleotide polymorphisms and haplotypes of TERT gene with longevity in Xinjiang Uygur population. Methods: A total of 361 Uygur subjects were selected including 112 individuals ≥90 years old and 249 controls. The tagging single nucleotide polymorphisms (tSNPs) were selected. The locus of telomerase reverse transcriptase (TERT) gene including rs2736098 (SNP1), rs2736100(SNP2), rs2853676(SNP3), rs10069690(SNP4), rs4975605 (SNP5), rs2075786(SNP6), rs2736118(SNP7), rs2853691 (SNP8) were genotyped by snapshot method and the haplotype distribution was estimated. Results: (1) The distributions of TTgenotype and T allele of SNP2 (SNP rs2736100) in longevity group were lower than in control group and P equals to 0.026, 0.009. The SNP rs2736100 was significantly associated with longevity (TT versus GG: P = 0.008, OR = 0.392, 95%CI: 0.193 ~ 0.796; GT + TT versus GG: P = 0.023, OR= 0.574, 95%CI: 0.355~ 0.928; T versus G: P = 0.009, OR= 0.652, 95%CI: 0.473 ~ 0.900). (2) The distributions of CC genotype and C allele of SNP6 (SNP rs2075786) in longevity group were lower than in control group and P equals to 0.044, 0.009. The SNP rs2075786 was significantly associated with longevity (CC versus TT: P = 0.013, OR = 0.426, 95%CI: 0.216 ~ 0.842; C versus T: P = 0.009, OR = 0.647, 95%CI: 0.465 ~ 0.899). (3) There was no statistically significant difference in the haplotype analysis. (4) Pulse pressure (PP) and pulse pressure index (PPI) in GT + TT genotype combination were markedly higher than in GG genotype of TERT SNP2 in longevity group, while PPI in TC + CC genotype was markedly higher than in TT genotype of TERT SNP6 in control group. Conclusion: Our study revealed that TERT gene rs2736100 and rs2075786 polymorphisms might be associated with longevity in Xinjiang Uygur population. TT genotype, T allele of rs2736100 and CC genotype, C allele of rs2075786 were the adverse factors of longevity. rs2736100 and rs2075786 might be associated with longevity through impacts on vascular function. doi:10.1016/j.ijcard.2011.08.737 0163 The association study of single nucleotide polymorphisms and haplotypes of VEGF gene with longevity in Xinjiang Uygur population XINJUAN XU, XIAOHUI LIANG, YULAN CHEN, ZHULEPIYA SIMAYI, SUHUA LI Department of Hypertension, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China Objective: We investigated the association of single nucleotide polymorphisms and haplotypes of VEGF gene with longevity in Xinjiang Uygur population. Methods: A case-control design was applied in this study. In brief, a total of 361 Uygur subjects were selected in the study including 112 individuals ≥90 years old and
S81
249 controls. The tagging single nucleotide polymorphisms (tSNPs) were selected. The locus of vascular endothelial growth factor (VEGF) gene including rs2146323 (SNP1), rs3024997 (SNP2), rs10434 (SNP3) were genotyped by snapshot method and the haplotype distribution was estimated. Results: (1) Three common SNPs of VEGF gene were chosen to be tagging SNPs. All polymorphisms were in Hardy-Weinberg equilibrium both in longevity and in control group. The frequencies of C and A allele of VEGF SNP1 in longevity group were 70.1%, 29.9% and 62.3%, 37.7% in the control group. The frequencies of SNP1 genotypes of CC, CA and AA in longevity group were 47.3%, 45.5%, 7.2% and 42.6%, 39.3%, 18.1% in control group, respectively. The distributions of AA genotype and A allele of SNP1 (SNP rs2146323) in longevity group were lower than in control group and P equals to 0.025, 0.041. The SNP rs2146323 was significantly associated with longevity (AA versus CC: P = 0.011, OR = 0.356, 95%CI: 0.156~ 0.808; A versus C: P = 0.041, OR = 0.704, 95%CI: 0.502 ~ 0.987). (2) The haplotype analysis revealed that the frequency of Hap1-CG was highest in both groups. The frequency of Hap1-CG was higher in longevity group than in control group, while the frequencies of Hap2-CA, Hap3-AG were lower in longevity group. There was no statistically significant difference. (3) The level of pulse pressure (PP) in CA + AA genotype combination was markedly higher than in CC genotype of VEGF SNP1 in control group. Conclusion: VEGF gene rs2146323 polymorphism might be associated with longevity. AA genotype and A allele were the adverse factors of longevity in Xinjiang Uygur population. rs2146323 might be associated with longevity through impacts on vascular function. doi:10.1016/j.ijcard.2011.08.738 0175 The neuropeptide catestatin promotes vascular smooth muscle cell proliferation through the Ca2+-calcineurin-NFAT signaling pathway XIAOXIA GUO, NINGLING SUN Department of Cardiology, People's Hospital, Peking University, Beijing, China Objective: We investigated the proliferative effect of catestatin (CST) on vascular smooth muscle cells (VSMCs) and furthermore researched its molecular mechanism. Methods: VSMCs were growth-arrested by incubating in DMEM containing 0.1% normal calf serum for 24 h. Growth-arrested cells were incubated for 24 h with concentrations of CST ranging from 10− 10–10− 6 mol/L. In additional experiments, growth-arrested VSMCs were treated with CST (1 μM) for 24 h (CST group), or incubated for 1 h with 1 μM cyclosporin A (CsA) prior to CST treatment (CST + CsA group). Cells treated with DMEM containing 0.1% normal calf serum or CsA alone were used as the control group or CsA group. Cell proliferation was assayed using Cell Counting kit-8 and cell cycle analysis was performed by flow cytometry. Intracellular calcium ion concentration ([Ca2+]i) was monitored by confocal microscope, and the expression of proliferative genes were measured by real-time RTPCR. Coimmunoprecipitation assay was carried for showing the interaction between calmodulin and calcineurin. Immunofluorescence experiments and western blots were performed for determining the intracellular localization of NFATc1. Results: Catestatin caused a dose-dependent induction of proliferation in VSMCs, exerting its maximal effect at 1 μM. In quiescent VSMCs, CST induced an increase in [Ca2+]i characterized by an initial Ca2+ spike followed by a sustained elevated plateau phase. The calcineurin inhibitor CsA decreases VSMC growth and proliferative gene expression induced by CST. CST favored the formation of calmodulin/calcineurin complexes and promoted translocation of NFATc1 from the cytoplasm to the nucleus, reflecting increased