Association of Dopamine-related Gene Alleles, Smoking Behavior and Decline in FEV₁ in Subjects with COPD: Findings from the Lung Health Study

Figures & data

Table 1.  Characteristics of male and female sustained quitters and continuing smokers.

Variable	Sustained quitters	Continuing smokers
Male
N (%)	187 (47.6)	206 (52.4)
Age	49.7 (0.5)*	47.6 (0.5)
Age started smoking	20.2 (0.2)†	14.5 (0.2)
Cigarettes/day at baseline	30.4 (1.0)†	41.2 (0.7)
FEV1,% predicted at baseline	80.0 (0.6)*	77.1 (0.6)
O'Conner slope at baseline	–9.0 (1.4), N = 183	–8.5 (1.0), N = 198
DRD2 A1+ allele, N (%)	67 (35.8)	81.0 (39.3)
DRD2 A1- allele, N (%)	120 (64.2)	125 (60.7)
DAT 9R+ allele, N (%)	92 (49.2)	95 (46.1)
DAT 9R- allele, N (%)	95 (50.8)	111 (53.9)
Female
N (%)	104 (45.6)	124 (54.4)
Age	49.8 (0.6)*	46.9 (0.6)
Age started smoking	20.4 (0.3)†	15.2 (0.1)
Cigarettes/day at baseline	25.4 (1.1)†	34.7 (0.9)
FEV1,% predicted at baseline	79.2 (0.9)	78.0 (0.8)
O'Conner slope at baseline	–20.7 (3.2), N = 102	–15.6 (2.0), N = 121
DRD2 A1+ allele, N (%)	38 (36.5)	48 (38.7)
DRD2 A1- allele, N (%)	66 (63.5)	76 (61.3)
DAT 9R+ allele, N (%)	55 (52.9)	51 (41.1)
DAT 9R- allele, N (%)	49 (47.1)	73 (58.9)

Values: mean (SE) except as noted.

FEV1,% predicted: forced expiratory volume in 1 second of predicted normal for their age, gender, height and race.

O'Conner slope: two-point slope to measure sensitivity to methacholine, calculated as the% drop in FEV1 at the highest concentration of methacholine used, divided by the cumulative concentration (or dose) of methacholine.

DRD2 A1+ allele consists of A1A1 or A1A2 genotype. DRD2 A1- allele consists of A2A2 genotype.

DAT 9R+ allele consists of 9R9R or 9R10R genotype. DAT 9R- allele consists of 10R 10R genotype.

*p <0.01; †p<0.0001.

Note: All p values are nominal since we did not adjust for multiple comparisons.

Table 2a.  Post-bronchodilator FEV1 over year 1 through year 5; results of mixed model analysis (males).

		Sustained Quitters		Continuing Smokers
Allele	N	Coefficient (SE)	p	Coefficient (SE)	P
DRD2 A1-		0.035 (0.05)	0.466	–0.016 (0.05)	0.741
DRD2 A1- * yr		–0.018 (0.01)	0.040	0.005 (0.01)	0.554
DAT 9R+		0.072 (0.05)	0.119	0.079 (0.05)	0.099
DAT 9R+ * yr		–0.018 (0.01)	0.029	–0.003 (0.01)	0.735
A1-/9R+		0.100 (0.07)	0.153	0.051 (0.07)	0.452
A1-/9R+ * yr		–0.038 (0.01)	0.003	0.002 (0.01)	0.856
A1-/9R- or A1+/9R+		0.006 (0.06)	0.924	–0.085 (0.06)	0.160
A1-/9R- or A1+.9R+ * yr		–0.018 (0.01)	0.125	0.001 (0.01)	0.909

Table 2b.  Post-bronchodilator FEV1 over year 1 through year 5; results of mixed model analysis (females).

		Sustained Quitters		Continuing Smokers
Allele	N	Coefficient (SE)	P	Coefficient (SE)	P
DRD2 A1-		0.007 (0.04)	0.862	–0.011 (0.04)	0.773
DRD2 A1- * yr		0.001 (0.01)	0.857	0.009 (0.01)	0.233
DAT 9R+		–0.113 (0.04)	0.005	0.015 (0.04)	0.682
DAT 9R+ * yr		0.004 (0.01)	0.587	–0.006 (0.01)	0.735
A1-/9R+		–0.108 (0.06)	0.071	–0.023 (0.05)	0.670
A1-/9R+ * yr		0.003 (0.01)	0.749	0.075 (0.05)	0.109
A1-/9R- or A1+/9R+		–0.041 (0.06)	0.461	–0.005 (0.01)	0.619
A1-/9R- or A1+.9R+ * yr		–0.005 (0.01)	0.633	0.002 (0.01)	0.851

Figure 1.  Predicted FEV1 (± SEM) from the mixed model at Year 1 to Year 5 in male sustained quitters stratified by the DRD2 A1+ or the DRD2 A1- allele (A), the DAT 9R+ or the DAT 9R- allele (B) and the combination of both the DRD2 A1- and DAT 9R+ or neither the DRD2 A1- nor the DAT 9R+ allele (C).

Table 3.  Mean slopes (± SEM) of change in FEV1% predicted per year from Year 1 through Year 5 by DRD2 and DAT alleles and combinations thereof, gender and smoking status.

	Quitters		Continuing Smokers
DRD2	A1+	A1-	A1+	A1-
Male	–0.02 (0.19)	–0.16 (0.14)*	–1.37 (0.20)	–1.34 (0.16)
Female	–0.59 (0.23)	–0.42 (0.18)	–1.64 (0.27)	–1.26 (0.16)
DAT	9R-	9R+	9R-	9R+
Male	–0.15 (0.17)	–0.65 (0.15)†	–1.27 (0.18)	–1.45 (0.17)
Female	–0.44 (0.19)	0.52 (0.20)	–1.30 (0.18)	–1.56 (0.25)
DRD2/DAT	A1+/9R-	A1-/9R+	A1+/9R-	A1-/9R+
Male	0.27 (0.32)	–0.86 (0.20)§	–1.33 (0.30)	–1.46 (0.24)
Female	–0.47 (0.23)	–0.42 (0.23)	–1.39 (0.33)	–1.28 (0.28)

*p = 0.014 compared with A1+.

†p = 0.030 compared with 9R-.

§p = 0.002 compared with A1+/9R-.

Note: All p-values are nominal since we did not adjust for multiple comparisons.

Figure 2.  Observed percent predicted FEV1 (± SEM) at baseline and Year 1 to Year 5 in male sustained quitters stratified by the DRD2 A1+ or the DRD2 A1- allele (A), the DAT 9R+ or the DAT 9R- allele (B) and the combination of both the DRD2 A1- and DAT 9R+ or neither the DRD2 A1- nor the DAT 9R+ allele (C).