rs1800775

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This is a upstream gene variant variant in the CETP gene.

Key Literature Trait Associations

HDL Cholesterol Levels

The rs1800775 variant is a promoter-region SNP in CETP (cholesteryl ester transfer protein) approximately 629 bp upstream of the transcription start site. The A allele reduces CETP expression, leading to higher HDL ('good') cholesterol levels. Higher HDL driven by reduced CETP activity was associated with exceptional longevity in centenarian studies, particularly among Ashkenazi Jewish centenarians. However, Mendelian randomization studies show the cardiovascular disease benefit is more modest than HDL levels alone would suggest.

Willer CJ et al. “Discovery and refinement of loci associated with lipid levels.” Nature Genetics 45(11):1274-1283 (2013)

Allele A

OR —

β -3.090

p 4.0e-93

N 188,577

Large GWAS

multi-ancestry

de Oliveira MV et al. “SHP-2 regulates myogenesis by coupling to FAK signaling pathway.” Febs Letters 583(18):2975-2981 (2009)

Allele A

OR —

β 2.500

p 1.0e-40

Large GWAS

Teslovich TM et al. “Biological, clinical and population relevance of 95 loci for blood lipids.” Nature 466(7307):707-713 (2010)

Allele A

OR —

p 1.0e-50

N 100,000

Large GWAS

European

Wakil SM et al. “A common variant association study reveals novel susceptibility loci for low HDL-cholesterol levels in ethnic Arabs.” Clinical Genetics 90(6):518-525 (2016)

Allele A

OR 1.31

p 3.4e-12

N 5,495

Large GWAS

Arab

Radovica I et al. “The association of common SNPs and haplotypes in CETP gene with HDL cholesterol levels in Latvian population.” Plos One (2013)

Allele A

OR —

p —

N 704

Preliminary work

European

Murray A et al. “Common lipid-altering gene variants are associated with therapeutic intervention thresholds of lipid levels in older people.” European Heart Journal (2009)

Allele A

OR —

p —

N 635

Preliminary work

European

Metabolic syndrome

A genome-wide association study in 10,093 Indian individuals identified rs1800775 as one of two primary CETP variants achieving genome-wide significance for metabolic syndrome in the replication phase. This association is biologically plausible given the well-established role of low HDL cholesterol as a core component of metabolic syndrome diagnosis. The finding has not been independently replicated in large non-Indian cohorts, so evidence remains at medium confidence.

Prasad G et al. “Genome-Wide Association Study of Metabolic Syndrome Reveals Primary Genetic Variants at CETP Locus in Indians.” Biomolecules (2019)

Allele C

OR —

p 5.0e-8

N 10,093

Small GWAS

South Asian

Myocardial infarction

A 2014 meta-analysis of 9 case-control studies (8,623 MI cases, 8,564 controls) found that the CETP rs1800775 C>A polymorphism may modestly increase MI risk, particularly in Caucasians. However, a larger 2023 meta-analysis of 70 studies (30,619 CAD cases, 31,836 controls) found no significant association between rs1800775 and coronary artery disease under any genetic model (allele, dominant, or recessive). The balance of evidence does not support an independent MI/CAD effect beyond HDL-C mediation.

Zhang R et al. “Association of the polymorphisms of the cholesteryl ester transfer protein gene with coronary artery disease: a meta-analysis.” Frontiers in Cardiovascular Medicine (2023)

Allele C

OR —

p 3.9e-1

N 62,455

Meta-analysis

multi-ancestry

Wang Q et al. “Seven functional polymorphisms in the CETP gene and myocardial infarction risk: a meta-analysis and meta-regression.” Plos One (2014)

Allele C

OR —

p —

N 17,187

Meta-analysis

multi-ancestry

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GWAS Catalog Trait Associations (6)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

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Research that mentions this SNP (1)

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Association of Cholesteryl Ester Transfer Protein Genotypes With CETP Mass and Activity, Lipid Levels, and Coronary Risk

Meta-analysisN=195,833Thompson A. et al.(2008)· JAMA

Systematic review of 92 lipid studies (113,833 participants) and 46 coronary disease studies (82,534 participants) examining CETP polymorphisms. TaqIB rs708272 A allele associated with 9.7% decreased CETP mass, 8.6% decreased CETP activity, 4.5% increased HDL-C (95% CI: 3.8%-5.2%), and weakly inverse association with coronary disease (OR 0.95, 95% CI: 0.92-0.99).

Traits studied:Apolipoprotein A-ICETP activityCETP massCoronary artery diseaseHDL cholesterol

rs1800775

Key Literature Trait Associations

HDL Cholesterol Levels

Metabolic syndrome

Myocardial infarction

GWAS Catalog Trait Associations (6)

Research that mentions this SNP (1)

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