Textbook of Personalized Medicine - Second Edition [2015]

481

Table 14.1

Gene polymorphisms relevant to cardiovascular disease management

Gene polymorphism

Effect

Signifi

cance for management

ACE (angiotensin converting enzyme)

Deletion allele (ACE D) is associated with increased

renin-angiotensin activation of the sympathetic nervous system

For determining responders vs non-responders to

β-blockers in heart failure

Adducin

Linked to hypertension sodium sensitivity

Response to diuretic therapy and sodium restriction

Angiotensin Gene (AGT)

Risk of hypertension

Identifying patients who respond to ACE inhibitors

Apolipoprotein (Apo)

ε^4

Risk of coronary artery disease. Response to statins

Treatment with simvastatin reduces mortality risk by 50 %

in Apo

ε4 carriers but only 13 % in Apo

ε4 non-carriers

ATP-binding cassette transporter 1

(ABCA1)

Regulates high-density cholesterol. Risk of coronary

artery disease

Target of drugs for controlling hypercholesterolemia

Cholesterol ester transferase protein

(CETP)

Progression of coronary atherosclerosis. Response

to statins

Predicts accelerated atherosclerosis and response to

pravastatin therapy in B1B1 carriers but not B2B2 carriers

Coronary Heart Disease 1 (CHD 1).

Lipid metabolism

Target for drug development

Epithelial sodium channel (

β subunit)

Linked to hypertension

Amiloride, a direct antagonist of this channel, is more

effective in individuals with this polymorphism

Factor VII

Risk of myocardial infarction

Indication for low-dose anticoagulation therapy

Interleukin-1 (IL-1)

Infl

ammatory response in blood vessels and heart disease Favorable response to statin therapy

PL

A2

polymorphism of gene encoding glycoprotein IIIb

Platelet aggregation and premature myocardial infarction Patients with this polymorphism should be treated with

aspirin, clopidrogrel and statins for prevention of coronary artery disease

P-selectin

Unstable angina pectoris

Helps in determining prognosis

SCN5A (encodes the Na ion channel

in the heart)

Cardiac arrhythmias

Suggests avoidance of Na-channel blockers in patients

with SCNA mutations

Dilated cardiac myopathy

Thrombospondin

Premature coronary artery disease

Indication for anti-platelet and antiinfl

ammatory therapy

WNK kinases

Linked to hypertension

Associate signaling pathways provide opportunity for

developing targeted antihypertensive therapy

© Jain PharmaBiotech

Introduction