Sirtuin/uncoupling protein gene variants and carotid plaque area and morphology

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Abstract

Background: Sirtuins and uncoupling proteins have been implicated in cardiovascular diseases by controlling oxidative stress.Aims: We sought to investigate the association of sirtuins and uncoupling proteins single nucleotide polymorphisms with total carotid plaque area and morphology measured by ultrasonographic gray scale median.Methods: We analyzed 1356 stroke-free subjects (60% women, mean age = 68 ± 9 years) from the Northern Manhattan Study. Multiple linear regression models were used to evaluate the association of 85 single nucleotide polymorphisms in 11 sirtuins/uncoupling protein genes with total plaque area and gray scale median after controlling for demographics, vascular risk factors (RFs), and population stratification. We investigated effect modifications of these relationship by gender and RFs and performed stratified analysis if the interaction effect had P <0·005.Results: Among individuals with present plaque (55%), the mean total plaque area was 20·3 ± 20·8 mm2 and gray scale median 90 ± 29. After adjustment, SIRT6 rs107251 was significantly associated with total plaque area (β = 0·30 per copy of T allele increase, Bonferroni-corrected P = 0·005). T allele carriers of rs1430583 in UCP1 showed a decreased gray scale median in women but not in men. The minor allele carriers of rs4980329 and rs12363280 in SIRT3 had higher gray scale median in men but not in women. Variants in UCP3 gene were significantly associated with higher mean gray scale median in individuals with dyslipidemia.Conclusion: Our findings suggest that polymorphisms in SIRT6/UCP1 genes may be important for increased carotid plaque burden and echodensity, but translation of these findings to an individual risk of cerebrovascular events needs further investigation. Significant associations of rs1430583 in women, rs12363280 in men, and rs1685354 in those with dyslipidemia also deserve further investigations.

Original languageEnglish (US)
Pages (from-to)1247-1252
Number of pages6
JournalInternational Journal of Stroke
Volume10
Issue number8
DOIs
StatePublished - Dec 1 2015

Fingerprint

Sirtuins
Alleles
Dyslipidemias
Genes
Single Nucleotide Polymorphism
Linear Models
Oxidative Stress
Cardiovascular Diseases
Stroke
Demography
Mitochondrial Uncoupling Proteins
Population

Keywords

  • atherosclerosis
  • carotid total plaque area
  • genetics
  • gray scale median
  • mitochondrial uncoupling proteins
  • sirtuins

ASJC Scopus subject areas

  • Neurology

Cite this

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title = "Sirtuin/uncoupling protein gene variants and carotid plaque area and morphology",
abstract = "Background: Sirtuins and uncoupling proteins have been implicated in cardiovascular diseases by controlling oxidative stress.Aims: We sought to investigate the association of sirtuins and uncoupling proteins single nucleotide polymorphisms with total carotid plaque area and morphology measured by ultrasonographic gray scale median.Methods: We analyzed 1356 stroke-free subjects (60{\%} women, mean age = 68 ± 9 years) from the Northern Manhattan Study. Multiple linear regression models were used to evaluate the association of 85 single nucleotide polymorphisms in 11 sirtuins/uncoupling protein genes with total plaque area and gray scale median after controlling for demographics, vascular risk factors (RFs), and population stratification. We investigated effect modifications of these relationship by gender and RFs and performed stratified analysis if the interaction effect had P <0·005.Results: Among individuals with present plaque (55{\%}), the mean total plaque area was 20·3 ± 20·8 mm2 and gray scale median 90 ± 29. After adjustment, SIRT6 rs107251 was significantly associated with total plaque area (β = 0·30 per copy of T allele increase, Bonferroni-corrected P = 0·005). T allele carriers of rs1430583 in UCP1 showed a decreased gray scale median in women but not in men. The minor allele carriers of rs4980329 and rs12363280 in SIRT3 had higher gray scale median in men but not in women. Variants in UCP3 gene were significantly associated with higher mean gray scale median in individuals with dyslipidemia.Conclusion: Our findings suggest that polymorphisms in SIRT6/UCP1 genes may be important for increased carotid plaque burden and echodensity, but translation of these findings to an individual risk of cerebrovascular events needs further investigation. Significant associations of rs1430583 in women, rs12363280 in men, and rs1685354 in those with dyslipidemia also deserve further investigations.",
keywords = "atherosclerosis, carotid total plaque area, genetics, gray scale median, mitochondrial uncoupling proteins, sirtuins",
author = "Chuanhui Dong and {Della Morte}, David and Digna Cabral and Liyong Wang and Blanton, {Susan H} and Seemant Chaturvedi and Sacco, {Ralph L} and Tatjana Rundek",
year = "2015",
month = "12",
day = "1",
doi = "10.1111/ijs.12623",
language = "English (US)",
volume = "10",
pages = "1247--1252",
journal = "International Journal of Stroke",
issn = "1747-4930",
publisher = "Wiley-Blackwell",
number = "8",

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TY - JOUR

T1 - Sirtuin/uncoupling protein gene variants and carotid plaque area and morphology

AU - Dong, Chuanhui

AU - Della Morte, David

AU - Cabral, Digna

AU - Wang, Liyong

AU - Blanton, Susan H

AU - Chaturvedi, Seemant

AU - Sacco, Ralph L

AU - Rundek, Tatjana

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Background: Sirtuins and uncoupling proteins have been implicated in cardiovascular diseases by controlling oxidative stress.Aims: We sought to investigate the association of sirtuins and uncoupling proteins single nucleotide polymorphisms with total carotid plaque area and morphology measured by ultrasonographic gray scale median.Methods: We analyzed 1356 stroke-free subjects (60% women, mean age = 68 ± 9 years) from the Northern Manhattan Study. Multiple linear regression models were used to evaluate the association of 85 single nucleotide polymorphisms in 11 sirtuins/uncoupling protein genes with total plaque area and gray scale median after controlling for demographics, vascular risk factors (RFs), and population stratification. We investigated effect modifications of these relationship by gender and RFs and performed stratified analysis if the interaction effect had P <0·005.Results: Among individuals with present plaque (55%), the mean total plaque area was 20·3 ± 20·8 mm2 and gray scale median 90 ± 29. After adjustment, SIRT6 rs107251 was significantly associated with total plaque area (β = 0·30 per copy of T allele increase, Bonferroni-corrected P = 0·005). T allele carriers of rs1430583 in UCP1 showed a decreased gray scale median in women but not in men. The minor allele carriers of rs4980329 and rs12363280 in SIRT3 had higher gray scale median in men but not in women. Variants in UCP3 gene were significantly associated with higher mean gray scale median in individuals with dyslipidemia.Conclusion: Our findings suggest that polymorphisms in SIRT6/UCP1 genes may be important for increased carotid plaque burden and echodensity, but translation of these findings to an individual risk of cerebrovascular events needs further investigation. Significant associations of rs1430583 in women, rs12363280 in men, and rs1685354 in those with dyslipidemia also deserve further investigations.

AB - Background: Sirtuins and uncoupling proteins have been implicated in cardiovascular diseases by controlling oxidative stress.Aims: We sought to investigate the association of sirtuins and uncoupling proteins single nucleotide polymorphisms with total carotid plaque area and morphology measured by ultrasonographic gray scale median.Methods: We analyzed 1356 stroke-free subjects (60% women, mean age = 68 ± 9 years) from the Northern Manhattan Study. Multiple linear regression models were used to evaluate the association of 85 single nucleotide polymorphisms in 11 sirtuins/uncoupling protein genes with total plaque area and gray scale median after controlling for demographics, vascular risk factors (RFs), and population stratification. We investigated effect modifications of these relationship by gender and RFs and performed stratified analysis if the interaction effect had P <0·005.Results: Among individuals with present plaque (55%), the mean total plaque area was 20·3 ± 20·8 mm2 and gray scale median 90 ± 29. After adjustment, SIRT6 rs107251 was significantly associated with total plaque area (β = 0·30 per copy of T allele increase, Bonferroni-corrected P = 0·005). T allele carriers of rs1430583 in UCP1 showed a decreased gray scale median in women but not in men. The minor allele carriers of rs4980329 and rs12363280 in SIRT3 had higher gray scale median in men but not in women. Variants in UCP3 gene were significantly associated with higher mean gray scale median in individuals with dyslipidemia.Conclusion: Our findings suggest that polymorphisms in SIRT6/UCP1 genes may be important for increased carotid plaque burden and echodensity, but translation of these findings to an individual risk of cerebrovascular events needs further investigation. Significant associations of rs1430583 in women, rs12363280 in men, and rs1685354 in those with dyslipidemia also deserve further investigations.

KW - atherosclerosis

KW - carotid total plaque area

KW - genetics

KW - gray scale median

KW - mitochondrial uncoupling proteins

KW - sirtuins

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DO - 10.1111/ijs.12623

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JO - International Journal of Stroke

JF - International Journal of Stroke

SN - 1747-4930

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