Table 3. Adjusted HRR and 95% CI of Incident Acute Coronary Events Associated with the COMT Genotype^*, Plasma tHcy and Serum Folate and Gene-Homocysteine and Gene-Folate Interactions.

Homocysteine, exposure definition
	High tHcy, COMT Val158Met or Val158Val		Low tHcy with COMT Met158Met		High tHcy with COMT Met158Met		Multiplicative interaction		Additive interaction
	HRR (95% CI)	p-value	HRR (95% CI)	p-value	HRR (95% CI)	p-value	HRRi (95% CI)	p-value	RERI (95% CI)
Model 1†	1.15 (0.60–2.20)	0.68	1.42 (0.75–2.68)	0.28	2.60 (1.35–5.03)	0.004	1.60 (0.60–4.25)	0.35	1.03 (−0.30–2.36)
Model 2‡	1.20 (0.62–2.30)	0.59	1.34 (0.70–2.56)	0.37	2.94 (1.50–5.76)	0.002	1.84 (0.68–4.95)	0.23	1.40 (−0.43–3.23)
Folate, exposure definition
	Low fol with COMT Val158Met or Val158Val		High fol with COMT Met158Met		Low fol with COMT M et158Met		Multiplicative interaction		Additive interaction
	HRR (95% CI)	p-value	HRR (95% CI)	p-value	HRR (95% CI)	p-value	HRRi (95% CI)	p-value	RERI (95% CI)
Model 1†	1.95 (1.05–3.63)	0.036	2.11 (1.11–4.01)	0.022	2.67 (1.28–5.59)	0.009	0.65 (0.25–1.73)	0.39	−0.39 (−2.60–1.83)
Model 2‡	2.05 (1.10–3.85)	0.025	2.07 (1.09–3.94)	0.027	2.80 (1.33–5.90)	0.007	0.66 (0.25–1.76)	0.41	−0.32 (−2.82–2.18)

Abbreviations: CI, confidence interval; COMT, catehol-O-methyltransferase; fol, serum folate concentration; HRR, hazard rate ratio; HRR_i, hazard rate ratio for a multiplicative interaction; RERI, relative excess risk for interaction; tHcy, serum total homocysteine concentration.

^* COMT low activity Met158Met is ‘at-risk’ genotype for this study. The comparison group for the HRRs in the first three columns of the table is the same, i.e. subjects with lower plasma tHcy (<11.3 µmol/L) with COMT Met158Val or Val158Val genotype.

^†Model 1 is adjusted for age and examination years.

^‡Model 2 is adjusted for age, examination years, serum HDL and LDL cholesterol and triglycerides, systolic blood pressure and smoking