rs708272

However, high HDL cholesterol, at least when combined with another HDL raising SNP (rs1800588), doesn’t appear to actually protect individuals from coronary artery disease, at least based on one study of ~800 Caucasian male patients. [PMID 18164013]

A similarly confusing picture emerges from a study of two populations of 10,000+ individuals each. The distribution of the CETP genotype was observed to be different in population-based studies compared with studies in populations selected by high cardiovascular risk, and contradictory results were seen when trying to figure out if the TaqIB SNP predicted whether drugs would lower plasma lipids or cardiovascular outcome.[PMID 18518852]

A meta-analysis concluded that there probably was a statistically significant, but weak, association for this SNP. For each rs708272(T) allele inherited, individuals had lower mean CETP mass (-9.7%; CI: -11.7% to -7.8%), lower mean CETP activity (-8.6%; CI: -13.0% to -4.1%), higher mean high-density lipoprotein cholesterol (HDL-C) concentrations (4.5%; CI: 3.8%-5.2%), and higher mean apolipoprotein A-I concentrations (2.4%; CI, 1.6%-3.2%). The combined per-allele odds ratios (ORs) for coronary disease were 0.95 (CI: 0.92-0.99).[PMID 18560005]

A prospective cohort study of 18,245 initially healthy American women over a 10-year period found similar results with respect to HDL-C levels and (inversely) risk of myocardial infarction; rs708272(T) was associated with a per-allele increase in HDL-C levels of 3.1 mg/dL and a concordant 24 percent lower risk of future myocardial infarction (age-adjusted HR 0.76, CI: 0.62-0.94).[PMID 20031564]

rs708272 has also been associated with reduced coronary heart disease risk in those drinking alcohol. More specifically, a 2014 study by Mehlig et al., ([PMID 25288221] studying 618 patients with CHD found that the B2B2 genotype, rs708272(T;T)), had a reduced risk (odds ratio 0.21) for CHD in intermediate vs low drinkers.

[PMID 20082485] Genetic variants involved in gallstone formation and capsaicin metabolism, and the risk of gallbladder cancer in Chilean women

[PMID 20489166] Cholesteryl Ester Transfer Protein Polymorphism (TaqIB) Associates With Risk in Postinfarction Patients With High C-Reactive Protein and High-Density Lipoprotein Cholesterol Levels

[PMID 22011848] Thrombospondin-4 polymorphism (A387P) predicts cardiovascular risk in postinfarction patients with high HDL cholesterol and C-reactive protein levels

[PMID 22073289] Interaction between Cholesteryl Ester Transfer Protein and Hepatic Lipase Encoding Genes and the Risk of Type 2 Diabetes: Results from the Telde Study

[PMID 22143414] Genetic variation in cholesterol ester transfer protein, serum CETP activity, and coronary artery disease risk in Asian Indian diabetic cohort

[PMID 12475937] Association testing by DNA pooling: an effective initial screen.

[PMID 17157861] Associations between HDL-cholesterol and polymorphisms in hepatic lipase and lipoprotein lipase genes are modified by dietary fat intake in African American and White adults.

[PMID 18275964] Low-density lipoprotein and high-density lipoprotein cholesterol levels in relation to genetic polymorphisms and menopausal status: the Atherosclerosis Risk in Communities (ARIC) Study.

[PMID 18549840] Cholesterol ester transfer protein, interleukin-8, peroxisome proliferator activator receptor alpha, and Toll-like receptor 4 genetic variations and risk of incident nonfatal myocardial infarction and ischemic stroke.

[PMID 18637884] Cholesteryl ester transfer protein (CETP) genetic variation and early onset of non-fatal myocardial infarction.

[PMID 18835593] Interactions between alcohol intake and the polymorphism of rs708272 on serum high-density lipoprotein cholesterol levels in the Guangxi Hei Yi Zhuang population.

[PMID 19041386] Genetic-epidemiological evidence on genes associated with HDL cholesterol levels: a systematic in-depth review.

[PMID 19263529] Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach.

[PMID 19336475] Integrated associations of genotypes with multiple blood biomarkers linked to coronary heart disease risk.

[PMID 19379518] Development of a fingerprinting panel using medically relevant polymorphisms.

[PMID 19913121] Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.

[PMID 20205905] Association of repeatedly measured intermediate risk factors for complex diseases with high dimensional SNP data.

[PMID 20565774] Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project.

[PMID 21146168] LPL polymorphism (D9N) predicts cardiovascular disease risk directly and through interaction with CETP polymorphism (TaqIB) in women with high HDL cholesterol and CRP.

[PMID 21316679] Associations between common genetic polymorphisms in the liver X receptor alpha and its target genes with the serum HDL-cholesterol concentration in adolescents of the HELENA Study.

[PMID 21423763] Interactions of the apolipoprotein A5 gene polymorphisms and alcohol consumption on serum lipid levels.

[PMID 23351584] Common variation in cholesteryl ester transfer protein: relationship of first major adverse cardiovascular events with the apolipoprotein B/apolipoprotein A-I ratio and the total cholesterol/high-density lipoprotein cholesterol ratio

[PMID 24283500] CETP gene polymorphisms and risk of coronary atherosclerosis in a Chinese population

[PMID 22715478] Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy.

[PMID 23533563] Novel risk factors for premature peripheral arterial occlusive disease in non-diabetic patients: a case-control study.

[PMID 23675527] The association of common SNPs and haplotypes in CETP gene with HDL cholesterol levels in Latvian population.

[PMID 25073458] CETP Gene Polymorphism in the Caucasian Population of West Siberia and in Groups Contrast by Total Serum Cholesterol Levels

[PMID 25366166] Review: CETP & CAD Risk

[PMID 25671407] A Systems Genetics Approach to Dyslipidemia in Children and Adolescents

Mechanisms:

• High CETP activity (G)

• Low CETP activity (A)

The “A” allele is associated with:

• Increased HDL levels [R]

• Low risk of myocardial infarction [R]

• High apolipoprotein concentrations [R]

• Increased risk of gallbladder cancer (Chilean women) [R]

• Increased risk of coronary artery disease [R]

• Lower HDL concentrations in postmenopausal women [R]

• Decreased risk of coronary atherosclerosis (Chinese) [R]

The “G” allele is associated with:

• Decreased levels of HDL [R]

This SNP is associated with (unknown which alleles):

• Protective effects of moderate alcohol consumption in terms of heart disease (men) [R]

Increased risk of type 2 diabetes [R]