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Gender Differences n Genetic Risk Profiles for Cardiovascular Disease
- Source :
- Silander, K, Alanne, M, Kristiansson, K, Saarela, O, Ripatti, S, Auro, K, Karvanen, J, Kulathinal, S, Niemela, M, Ellonen, P, Vartiainen, E, Jousilahti, P, Saarela, J, Kuulasmaa, K, Evans, A, Perola, M, Salomaa, V & Peltonen, L 2008, ' Gender Differences n Genetic Risk Profiles for Cardiovascular Disease ' PLoS ONE, vol. 3(10), no. 10, e3615, pp. 1-15 . DOI: 10.1371/journal.pone.0003615, PLoS ONE, PLoS ONE, Vol 3, Iss 10, p e3615 (2008)
- Publication Year :
- 2008
-
Abstract
- BackgroundCardiovascular disease (CVD) incidence, complications and burden differ markedly between women and men. Although there is variation in the distribution of lifestyle factors between the genders, they do not fully explain the differences in CVD incidence and suggest the existence of gender-specific genetic risk factors. We aimed to estimate whether the genetic risk profiles of coronary heart disease (CHD), ischemic stroke and the composite end-point of CVD differ between the genders.Methodology/principal findingsWe studied in two Finnish population cohorts, using the case-cohort design the association between common variation in 46 candidate genes and CHD, ischemic stroke, CVD, and CVD-related quantitative risk factors. We analyzed men and women jointly and also conducted genotype-gender interaction analysis. Several allelic variants conferred disease risk for men and women jointly, including rs1801020 in coagulation factor XII (HR = 1.31 (1.08-1.60) for CVD, uncorrected p = 0.006 multiplicative model). Variant rs11673407 in the fucosyltransferase 3 gene was strongly associated with waist/hip ratio (uncorrected p = 0.00005) in joint analysis. In interaction analysis we found statistical evidence of variant-gender interaction conferring risk of CHD and CVD: rs3742264 in the carboxypeptidase B2 gene, p(interaction) = 0.009 for CHD, and rs2774279 in the upstream stimulatory factor 1 gene, p(interaction) = 0.007 for CHD and CVD, showed strong association in women but not in men, while rs2069840 in interleukin 6 gene, p(interaction) = 0.004 for CVD, showed strong association in men but not in women (uncorrected p-values). Also, two variants in the selenoprotein S gene conferred risk for ischemic stroke in women, p(interaction) = 0.003 and 0.007. Importantly, we identified a larger number of gender-specific effects for women than for men.Conclusions/significanceA false discovery rate analysis suggests that we may expect half of the reported findings for combined gender analysis to be true positives, while at least third of the reported genotype-gender interaction results are true positives. The asymmetry in positive findings between the genders could imply that genetic risk loci for CVD are more readily detectable in women, while for men they are more confounded by environmental/lifestyle risk factors. The possible differences in genetic risk profiles between the genders should be addressed in more detail in genetic studies of CVD, and more focus on female CVD risk is also warranted in genome-wide association studies.
- Subjects :
- Male
Pathology
Cardiovascular Disorders/Coronary Artery Disease
312 Clinical medicine
Disease
030204 cardiovascular system & hematology
Cohort Studies
chemistry.chemical_compound
0302 clinical medicine
Risk Factors
Prevalence
311 Basic medicine
Genetics and Genomics/Medical Genetics
Medicine(all)
Sex Characteristics
0303 health sciences
318 Medical biotechnology
Multidisciplinary
Agricultural and Biological Sciences(all)
Incidence (epidemiology)
Middle Aged
3. Good health
Cardiovascular Diseases
Medicine
Female
Research Article
Cohort study
Sex characteristics
Adult
medicine.medical_specialty
Science
Cardiovascular Disorders
education
Genetics and Genomics/Complex Traits
Polymorphism, Single Nucleotide
03 medical and health sciences
medicine
Humans
Genetic Predisposition to Disease
cardiovascular diseases
Allele
Aged
030304 developmental biology
business.industry
Cholesterol
Biochemistry, Genetics and Molecular Biology(all)
Gene Expression Profiling
Case-control study
217 Medical engineering
Human genetics
chemistry
Case-Control Studies
Cardiovascular Disorders/Cardiovascular Diseases in Women
Public Health and Epidemiology/Epidemiology
118 Biological sciences
business
Demography
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Silander, K, Alanne, M, Kristiansson, K, Saarela, O, Ripatti, S, Auro, K, Karvanen, J, Kulathinal, S, Niemela, M, Ellonen, P, Vartiainen, E, Jousilahti, P, Saarela, J, Kuulasmaa, K, Evans, A, Perola, M, Salomaa, V & Peltonen, L 2008, ' Gender Differences n Genetic Risk Profiles for Cardiovascular Disease ' PLoS ONE, vol. 3(10), no. 10, e3615, pp. 1-15 . DOI: 10.1371/journal.pone.0003615, PLoS ONE, PLoS ONE, Vol 3, Iss 10, p e3615 (2008)
- Accession number :
- edsair.doi.dedup.....d47c1976b937d8686317d821584a9018