Dataset Information

Interaction between a common variant in FADS1 and erythrocyte polyunsaturated fatty acids on lipid profile in Chinese Hans.

ABSTRACT: Little is known about the associations of FADS1 genetic variants with circulating levels of PUFA and lipids in Asian populations who have a different dietary pattern and dyslipidemia prevalence compared with Western populations. In a population-based sample of 3,210 unrelated Han Chinese living in Beijing and Shanghai, we examined a FADS1 genetic variant, rs174550, in relation to blood PUFA and lipid levels. C-allele of rs174550 was significantly associated with levels of erythrocyte PUFAs in upstream and downstream pathways of delta-5 desaturase (D5D) (P ? 0.003). Moreover, rs174550 C-allele was associated with a lower HDL cholesterol level (P = 0.02) in total population and a higher triglyceride level (P = 0.0002) in Beijing residents. Interestingly, erythrocyte levels of 18:2n-6 and 18:3n-3 modified the effect of rs174550 on HDL cholesterol level: stronger associations between rs174550 C-allele and lower HDL cholesterol levels were exhibited when erythrocyte 18:2n-6 or 18:3n-3 level was low (P for interaction = 0.02 and 0.03, respectively). These data suggested that FADS1 genetic variant was associated with circulating PUFA and lipid levels and that its effect on HDL cholesterol might depend on PUFA status in the Han Chinese population.

SUBMITTER: Zhu J

PROVIDER: S-EPMC3622339 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Interaction between a common variant in FADS1 and erythrocyte polyunsaturated fatty acids on lipid profile in Chinese Hans.

Zhu Jingwen J Sun Qi Q Zong Geng G Si Yuan Y Liu Chen C Qi Qibin Q Ye Xingwang X Sun Liang L Sheng Hongguang H Li Huaixing H Lin Xu X

Journal of lipid research 20130208 5

Little is known about the associations of FADS1 genetic variants with circulating levels of PUFA and lipids in Asian populations who have a different dietary pattern and dyslipidemia prevalence compared with Western populations. In a population-based sample of 3,210 unrelated Han Chinese living in Beijing and Shanghai, we examined a FADS1 genetic variant, rs174550, in relation to blood PUFA and lipid levels. C-allele of rs174550 was significantly associated with levels of erythrocyte PUFAs in up ...[more]

PMID: 23396965

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Project description:ImportanceAortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets.ObjectiveTo identify novel genetic loci and pathways associated with AS.Design, setting, and participantsThis genome-wide association study used a case-control design to evaluate 44 703 participants (3469 cases of AS) of self-reported European ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (from January 1, 1996, to December 31, 2015). Replication was performed in 7 other cohorts totaling 256 926 participants (5926 cases of AS), with additional analyses performed in 6942 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Follow-up biomarker analyses with aortic valve calcium (AVC) were also performed. Data were analyzed from May 1, 2017, to December 5, 2019.ExposuresGenetic variants (615 643 variants) and polyunsaturated fatty acids (ω-6 and ω-3) measured in blood samples.Main outcomes and measuresAortic stenosis and aortic valve replacement defined by electronic health records, surgical records, or echocardiography and the presence of AVC measured by computed tomography.ResultsThe mean (SD) age of the 44 703 GERA participants was 69.7 (8.4) years, and 22 019 (49.3%) were men. The rs174547 variant at the FADS1/2 locus was associated with AS (odds ratio [OR] per C allele, 0.88; 95% CI, 0.83-0.93; P = 3.0 × 10-6), with genome-wide significance after meta-analysis with 7 replication cohorts totaling 312 118 individuals (9395 cases of AS) (OR, 0.91; 95% CI, 0.88-0.94; P = 2.5 × 10-8). A consistent association with AVC was also observed (OR, 0.91; 95% CI, 0.83-0.99; P = .03). A higher ratio of arachidonic acid to linoleic acid was associated with AVC (OR per SD of the natural logarithm, 1.19; 95% CI, 1.09-1.30; P = 6.6 × 10-5). In mendelian randomization, increased FADS1 liver expression and arachidonic acid were associated with AS (OR per unit of normalized expression, 1.31 [95% CI, 1.17-1.48; P = 7.4 × 10-6]; OR per 5-percentage point increase in arachidonic acid for AVC, 1.23 [95% CI, 1.01-1.49; P = .04]; OR per 5-percentage point increase in arachidonic acid for AS, 1.08 [95% CI, 1.04-1.13; P = 4.1 × 10-4]).Conclusions and relevanceVariation at the FADS1/2 locus was associated with AS and AVC. Findings from biomarker measurements and mendelian randomization appear to link ω-6 fatty acid biosynthesis to AS, which may represent a therapeutic target.

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Dataset Information

Interaction between a common variant in FADS1 and erythrocyte polyunsaturated fatty acids on lipid profile in Chinese Hans.

Publications

Interaction between a common variant in FADS1 and erythrocyte polyunsaturated fatty acids on lipid profile in Chinese Hans.

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