Genetics of coronary heart disease with reference to ApoAI-CIII-AIV gene region

Table 1 Prevalence of coronary artery disease in different Indian surveys

City	Prevalence	Ref.
Urban population
Chandigarh	(6.60%)	Sarvotham et al[49]
Rohtak	(3.80%)	Gupta et al[50]
Jaipur	(7.60%)	Gupta et al[51]
Delhi	(9.70%)	Chada et al[52]
Rural population
Jaipur	(3.50%)	Gupta et al[53]
Ludhiana	(3.08%)	Wander et al[54]
South Indians
Tamil Nadu	(14.30%)	Ramachandran et al[55]
Tamil Nadu	(11.00%)	Mohan et al[56]
Migrant Indians
London, United Kingdom	(17.00%)	Bahl et al[57]
Illinois, United States	(10.00%)	Enas et al[3]

Table 2 Genetic and environmental risk factors for coronary heart disease

Risk factors with a significant genetic component (heritability)

Elevated LDL and VLDL cholesterol (40%-60%)

Low HDL cholesterol (45%-75%)

Elevated triglycerides (40%-80%)

Increased body mass index (25%-60%)

Elevated systolic blood pressure (50%-70%)

Elevated diastolic blood pressure (50%-65%)

Elevated lipoprotein(a) levels (90%)

Elevated homocysteine levels (45%)

Type 2 diabetes mellitus (40%-80%)

Elevated fibrinogen (20%-50%)

Elevated C-reactive protein (40%)

Elevated homocysteine levels (45%)

Gender

Age

Family history

Environmental risk factors

Smoking

Diet

Exercise

Infection

Foetal environment

Air pollution (particulates)

Risk factors for coronary heart disease can be subdivided into those that are determined significantly by genetic differences and those that are largely environmental (Based on Lusis et al[58] 2004). VLDL: Very low density lipoprotein; LDL: Low density lipoprotein; HDL: High density lipoprotein.

Table 3 Example of association studies of factors involved in inflammation and cell signalling with coronary artery disease and/or myocardial infarction

Gene	Polymorphism	Ref.	Suggested results
CRP	1059G/C	Zee et al[59]	No significant association with non-fatal MI, stroke or cardiovascular death
ICAM-1	Lys-469-glu	Jiang et al[60]	Association with MI and CAD
E-selectin	Ser-128-Arg, Leu-554-phe, G98T	Wenzel et al[61]	Associated with angiographic proof of severe CAD in patients < 50 yr
	Ser-128-Arg, G98T	Herrmann et al[62]	No association with MI
		Zheng et al[63]	T allele more common in younger patients with angiographic CAD
	Ser-128-Arg	Ye et al[64]	Association with early-onset CAD
P-selectin	Pro715	Herrmann et al[65], Kee et al[66]	Possibly has a protective role from MI
	S290N, N562D, V599L, T715P, T741T	Tregouet et al[67]	Protective effect of the P715; S290N and N562D associated with MI, when carried by certain haplotype
	C-2123G, A-1969G, Thr715Pro	Barbaux et al[68]	Polymorphisms associated with P-selectin levels but not with MI
TNF-αandβ	-863C/A, -308G/A (TNF-α), 252G/A (TNF-β)	Koch et al[69]	No association of TNF or IL-10 polymorphisms with MI or CAD
TNF-α	Five polymorphisms	Herrmann et al[65]	No association to MI or CAD
TNF-αandβ	TNF- α 308 G/A ,	Padovani et al[70]	No association to MI
	TNF- β 252 A/G
TNF-αandβ	TNF- β 308 G/A , TNF- β 252 A/G	Keso et al[71]	No association to old MI by autopsy or CAD
TNF-α	308 G/A	Francis et al[72]	No association to angiographic CAD
IL-1 cluster	IL-1α (-889), IL-1b (-511),	Francis et al[72]	No association to angiographic CAD
	IL-1β (+3953), IL-1RA intron 2 VNTR		IL-1RA VNTR allele 2 associated with single-vessel CAD
IL-1-RA	IL-1RA intron 2 VNTR	Manzoli et al[73]	No clear-cut association to CAD or MI
IL-1 cluster	IL-1β 511 C/T, IL-1RA intron 2 VNTR	Vohnout et al[74]	No association to angiographic CAD with either polymorphisms
IL-1-RA	IL 1RN-VNTR	Zee et al[75]	No association with risk for future MI
IL-1β, IL-RA	IL-1β 511 C/T, IL-1RA intron 2 VNTR	Momiyama et al[76]	IL-1 β (-511)C/C and IL-1Ra (intron 2)2-or 3- repeat allele both associated with CAD, association with MI only in patient who are seropositive for Chlamydia pneumoniae
IL-6	IL-6 G (-174)C promoter polymorphism	Nauck et al[77]	No association with the risk for CAD or MI
	-174 (G/C), -572 (G/C), -596 (G/A), +528 I/D	Georges et al[78]	-174 C associated with MI (OR = 1.34)-174 C more frequent in patients with two or fewer stenosed vessels than in patients with three vessel lesions
IL-10	3 IL-10 promotor polymorphisms (1082G/A, - 819C/T and -592C/A)	Koch et al[69]	No association with MI or CAD
	7 polymorphisms	Donger et al[79]	No association with risk for MI
TGF-β1	29 T/C	Yokota et al[80]	T allele is a risk factor for MI in middle-aged Japanese men
	-509T	Wang et al[81]	No association with CAD
	7 polymorphisms	Cambien et al[82]	No association with degree of angiographic CAD, Pro25 allele associated with MI in some regions.
Stromelysin(MMP-3)	5 polymorphisms	Syrris et al[83]	No association of either polymorphisms with CAD
	5A-117/6A promoter polymorphism (5A/6A)	Schwarz et al[84]	No association with the risk for MI, 6A allele marker for progression of CAD
	5A/6A	Terashima et al[85]	5A allele associated with risk for MI
	5A/6A	Kim et al[86]	5A allele associated with stable angina
	5A/6A	Humphries et al[87]	6A genotypes at greater risk for CAD related events in nonsmokers, 5A/5A genotypes amplifies risk in smokers
	5A/6A	Ye et al[88]	Homozygosis for 6A associated with greater progression of angiographic CAD
PECAM-1(CD31)	Val 125Leu, Asn563Ser and Gly670Arg	Sasaoka et al[89]	563Ser/Ser and 670Arg/Arg genotypes associated with MI
	Val 125Leu, Asn563Ser	Wenzel et al[90]	125 Val and 563Asn associated with early onset of CAD (< 50 yr)
	Leu 125Val, Ser563Asn	Song et al[91]	125Val and 563Asn associated with CAD
	Val125Leu	Gardemann et al[92]	No association with MI; weak association of Val125 with CAD in low-risk patients without HTN or DM (OR = 1.54; 95%CI: 1.03-2.3)

CRP: C-reactive protein; DM: Diabetes mellitus; HTN: Hypertension; ICAM: Intercellular adhesion molecule; IL: Interleukin; MI: Myocardial infarction; MMP: Matrix metalloproteinase; PECAM: Platelet endothelial cell adhesion molecule; TGF: Transforming growth factor; TNF: Tumor necrosis factor; VNTR: Variable number of tandem repeats.