Table 2.

Mendelian disorders relevant to atherosclerosis

Trait	Disease (gene)	Characteristics
Elevated LDL/VLDL levels	Familial hypercholesterolaemia (LDL receptor)5	Dominant disorder characterized by very high LDL-cholesterol levels and early CHD
	Familial defective apoB-100 (apoB)5	Dominant disorder due to apoB mutations that affect binding to LDL receptor; less severe than FH
Low HDL levels	ApoAI deficiency (apoAI)5	In the homozygous state, null mutations of apoAI result in the virtual absence of HDL and early CHD
	Tangier disease (ABC1 transporter)45,46	This recessive disorder results in the inability of cells to export cholesterol and phospholipids, resulting in very low levels of HDL
Coagulation	Various genetic disorders of haemostasis5	Unlike rare disorders of lipid metabolism where atherosclerotic disease is a primary manifestation, genetic disorders of haemostasis usually present either as increased risk of bleeding or thrombosis (usually venous), with no outstanding effect on atherogenesis
Elevated homocysteine	Homocystinuria (cystathionine β-synthetase)36	Recessive metabolic disorder resulting in very high levels of homocysteine and severe occlusive vascular disease
Diabetes, type 2	MODY1 (hepatocyte nuclear factor 4α)5, MODY2 (glucokinase)5, MODY3 (hepatocyte nuclear factor 1α)5	MODY1, 2, and 3 are characterized by the development of non-insulin dependent diabetes mellitus in young adults
Hypertension	Glucorticoid-remediable aldosteronism (hybrid gene from crossover of 11-β-hydroxylase and aldosterone synthase)60	Dominant disorder with early-onset hypertension and stroke
	Liddle’s syndrome (epithelial sodium channel)60	Dominant disorder with hypertension and metabolic alkalosis
	Mineralocorticoid receptor47	Early-onset hypertension associated with pregnancy