Peroxisome proliferator-activated receptor gamma-2 P12A polymorphism and risk of acute myocardial infarction, coronary heart disease and ischemic stroke: A case-cohort study and meta-analyses

Figures & data

Table 4 Characteristics of studies included in the meta - analysis

	Author	Year of publication	Country	Study design	Cases			Controls			Effect measurement (With 95% CI; P value)			Mean age ± SD (years)		Sex	End point	Allele frequency 12Ala	P (HWE)
					P/P	P/A	A/A	P/P	P/A	A/A	Dominant	Recessive	Additive	Cases	Controls
1	Vos et al	^Citation2000	Netherlands	Case-control	437	105	21	512	122	12	1.1 (0.84–1.45; 0.49)	2.0 (1.0–4.2; 0.049)	1.2 (0.9–1.5; 0.19)	No data	No data	M	MI	0.113	0.14
2	Bluher et al	^Citation2002	Germany	Cross-sectional	174	23	4	140	22	2	0.91 (0.50–1.6; 0.74)	1.6 (0.3–9.09; 0.56)	0.97 (0.56–1.7; 0.91)	67.1 (43–91)a	63.3 (33–87)a	M/F	CHD	0.079	0.30
3	Ridker et al	^Citation2003	USA	Nested Case-control	425	92	6	1610	451	31	0.77 (0.60–0.98; 0.03)	0.76 (0.32–1.8; 0.55)	0.79 (0.63–0.99; 0.04)	58.3	58.4	M	MI	0.123	0.93
4	Tobin et al	^Citation2004	UK	Case-control	434	103	10	381	120	4	0.80 (0.60–1.07; 0.13)	2.33 (0.73–7.5; 0.14)	0.87 (0.67–1.14; 0.31)	61.9 ± 9.2	58.6 ± 10.7	M/F	MI	0.127	0.09
5	Doney et al	^Citation2004	Scotland	Cohort		35			1141		0.21 (0.06–0.69; 0.01)	No data	No data	No data	64.4 ± 11.6	M/F	MI	0.111	0.69
6	Pischon et al (NHS study)	^Citation2005	USA	Cohort	187	54	4	386	93	6	1.2 (0.84-1.7; 0.31)	1.3 (0.37–4.7; 0.66)	1.19 (0.85–1.7; 0.30)	60.4 ± 0.4	60.3 ± 0.3	F	CHD	0.108	0.88
7	Pischon et al (HPFS study)	^Citation2005	USA	Cohort	187	59	4	407	91	4	1.44 (1.0-2.07; 0.05)	2.02 (0.5–8.16; 0.31)	1.4 (1.01–1.97; 0.042)	65.2 ± 0.5	65.1 ± 0.4	M	CHD	0.099	0.66
8	Li et al	^Citation2006	China	Case-control	195	23	0	588	36	2	1.83 (1.06-3.1; 0.03)	0.57 (0.0–4.9; 0.41)	1.69 (0.98–2.8; 0.057)	65.0 ± 11	62.1 ± 8.2	M/F	MI	0.032	0.08
9	Zafarmand et al (present study)	^Citation2007	Netherlands	Case-cohort	167	41	3	1143	346	30	0.82 (0.58–1.17; 0.27)	0.72 (0.22–2.37; 0.58)	0.81 (0.59–1.12; 0.20)	61 ± 6	57± 6	F	CHD, MI	0.134	0.52

Abbreviations: CHD, coronary heart disease; MI, myocardial infarction; HWE, Hardy – Weinberg equilibrium.

a Notes: Range of age (year).

Table 1 Baseline characteristics of the sub-cohort according to genotype, and clinical characteristics of CHD cases and controls in the Prospect – Epic cohort

	sub-cohort (N = 1519)			p-valueb	CHD cases	Sub-cohort	p-valuec
	P12P	P12A	A 12A
N total	1143	346	30	-	211	1519	-
Age at intake (yr)a	57.2 ± 6.1	57.1 ± 6.0	56.1 ± 5.4	0.63	60.5 ± 5.9	57.1 ± 6.1	<0.01
Body mass index (kg/m^2)a	25.8 ± 3.9	25.8 ± 4.1	26.4 ± 3.6	0.69	26.8 ± 3.9	25.8 ± 4.0	<0.01
Weight (kg)a	69.5 ±11.2	69.9 ±11.8	72.7 ±11.6	0.28	71.1 ± 11.3	69.7 ± 11.3	0.08
Height (cm)a	164.2 ± 6	164.5 ± 5	165.8 ± 6	0.24	162.8 ± 6	164.3 ± 6	0.01
Waist to hip ratioa	0.78 ± 0.05	0.78 ± 0.05	0.79 ± 0.06	0.56	0.81 ± 0.06	0.79 ± 0.06	<0.01
Hypertension (%)d	34.6	29.8	33.3	0.25	51.7	33.4	<0.01
Systolic blood pressure (mm Hg)a	133.1 ± 20.2	131.3 ± 19.3	132.9 ± 19.5	0.35	143.3 ± 22.3	132.7 ± 20.0	<0.01
Diastolic blood pressure (mm Hg)a	79.1 ± 10.6	78.7 ± 10.5	79.8 ± 10.6	0.80	81.6 ± 10.7	79.0 ± 10.6	<0.01
Presence of diabetes (%)	2.3	2.0	3.3	0.88	5.7	2.2	<0.01
Presence of hypercholesterolemia (%)	4	4	0	0.53	11.4	3.9	<0.01
Current alcohol consumption (%)	87.9	88.3	88.9	0.97	80.9	88.0	<0.01
Smoking status (%) Past	34.6	35.3	33.3	0.96	26.1	34.8	<0.01
Current	23.1	21.4	33.3	0.31	34.1	22.9	<0.01
Pack- yearse	6.8 ± 9.5	6.1 ± 9.1	7.9 ± 11.3	0.38	9.8 ± 11.4	6.7 ± 9.5	<0.01
Total cholesterol (mmol/L)a	5.9 ± 1	5.8 ± 1	5.9 ± 1.1	0.14	6.4 ± 1	5.9 ± 1	<0.01
HDL cholesterol (mmol/L)a	1.6 ± 0.4	1.6 ± 0.4	1.5 ± 0.4	0.70	1.4 ± 0.3	1.6 ± 0.4	<0.01
LDL cholesterol (mmol/L)a	3.9 ± 0.9	3.9 ± 0.9	4.0 ± 1.1	0.28	4.4 ± 1	3.9 ± 0.9	<0.01
Serum glucose (mmol/L)a	4.5 ± 1.4	4.5 ± 1.5	4.2 ± 1.5	0.31	5.1 ± 2.5	4.5 ± 1.4	<0.01

Notes:

a Mean ± standard deviation;

b Comparison of risk factors across genotypes, using the ANOVA F test (continuous variables) and the χ² statistic (categorical variables);

c Comparison of risk factors across disease status, using the independent samples t-test (continuous variables) and the χ² statistic (categorical variables);

d Defi ned as a systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg and/or questionnaire positive;

e The number of packs of cigarettes smoked per day by the number of years the person has smoked.

Abbreviations: HDL, high-density lipoprotein; LDL, low-density lipoprotein; CHD, coronary heart disease (ICD 410–414).

Table 2 Genotype and allele frequencies of the polymorphism among AMI, CHD, and ischemic stroke cases and sub-cohort of the Prospect – Epic cohort

Genotype/allele	Acute myocardial infarction		Coronary heart disease		Ischemic stroke		Sub-cohort
	No.	%	No.	%	No.	%	No.	%
No. of subjects	71		211		49		1519
Genotype
P/P	61	85.9	167	79.1	38	77.6	1143	75.2
P/A	10	14.1	41	19.4	10	20.4	346	22.8
A/A	0	0.0	3	1.4	1	2	30	2
Allele
Pro	132	93.0	375	88.9	86	87.8	2632	86.6
Ala	10	7.0	47	11.1	12	12.2	406	13.4
	χ^2 = 4.77		χ^2 = 1.61		χ^2 = 0.10
	Df = 1		df = 1		df = 1
	p = 0.03		p = 0.20		p = 0.75

Table 3 Hazard ratios of cardiovascular events under different genetic models for P12A polymorphism in PPARG gene in the Prospect – Epic cohort

Different events Model	Inheritance Model	Hazard ratio	95% CI	p-value
Acute myocardial infarction	Dominant	0.51	0.26–1.00	0.05
	Recessive	0.34	0.00–2.68	0.47
	Additive	0.49	0.26–0.94	0.03
Coronary heart disease	Dominant	0.82	0.58–1.17	0.27
	ecessive	0.72	0.22–2.37	0.58
	Additive	0.81	0.59–1.12	0.20
Ischemic stroke	Dominant	0.90	0.46–1.78	0.77
	Recessive	1.03	0.14–7.74	0.97
	Additive	0.90	0.49–1.67	0.75
All ischemic envents	Dominant	0.85	0.62–1.17	0.31
	Recessive	0.78	0.27–2.22	0.63
	Additive	0.83	0.62–1.11	0.21

Figure1 Meta-analyses of AMI risk under the different genetic models

These forest plots show the overall odds ratio for 6 studies included in the meta-analysis under the dominant, recessive, and additive models respectively. Doney and colleagues (2004) did not provide data for recessive and additive models. Size of cubes represents weight of each study.

Figure 2 Meta-analyses of CHD risk under the different genetic models

These forest plots show the overall odds ratio for 9 studies included in the meta-analysis under the dominant, recessive, and additive models respectively. Doney and colleagues (2004) did not provide data for recessive and additive models. Size of cubes represents weight of each study.

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