CHRNA5/CHRNA3 Locus Associates with Increased Mortality among Smokers

Figures & data

Table 1. Background characteristics of the COPD patients and male smokers.

	COPD patients	Male smokers
N	575	1911
% of men	64.70%	100%
Recruitment year	2005–2007	1991–1992
Recruitment age, mean (SD)	63.8 (7.0)	63.5 (5.0)
Age at death, mean (SD)	68.5 SD 6.2)	72.6 (6.8)
Dead (%)	114 (15.4)	1485 (77.7) †
Pack-years, mean (SD)	40.9 (23.3)	41.5 (19.3)
Former smokers (%)	348 (60.5)	465 (24.3)
MAF for rs1051730	38.40%	34.70%
BMI, mean (SD)	26.9 (5.4)	26.4 (3.9)^*
Co-morbidities
Cardiovascular disease	165 (28.7%)
Psychiatric disease	137 (24.0%)
Alcohol abuse	101 (17.6%)	184 (10.2%)^*
Diabetes	90 (15.7%)
Cancer	59 (10.3%)
Lung Functions
FEV1% of predicted, mean (SD)	58 (19)
FEV1/FVC, mean (SD)	0,64 (0,18)

^*BMI and Alcohol abuse calculated at the enrollment to the study in 1985–1988.

^†Data gathered from the population statistics at year 2010.

Table 2. Risk factors for increased mortality in the study cohorts.

	COPD cohort			Male Smokers
	N	Crude HR (CI)	Adjusted HR (CI)	N	Crude HR (CI)	Adjusted HR (CI)
SNP, additive model
Major homozygote	216	1.00	1.00	817	1.00	1.00
Heterozygote	276	1.19 (0.74-1.91)	1.08 (0.65-1.82)	860	1.15 (1.03-1.28)^*	1.17 (1.04-1.31)^*^*
Minor homozygote	83	2.16 (1.22-3.82)^*^*	2.64 (1.41-4.93)^*^*	234	1.26 (1.07-1.48)^*^*	1.23 (1.04-1.45)^*
Men	372	1.00	1.00
Women	203	0.61 (0.42-0.90)^*	0.76 (0.45-1.30)
Pack-years >40 yrs	357	1.29 (0.90-1.85)	1.14 (0.72-1.79)	813	1.24 (1.12-1.38)^*^*	1.14 (1.03-1.27)^*
Smoking cessation	348	0.38 (0.26-0.55)^*^*	0.51 (0.32-0.83)^*^*	465	0.79 (0.70-0.89)^*^*	0.83 (0.73-0.95)^*^*
BMI
Normal (≤25)†	235	1.00	1.00	719	1.00	1.00
25-30	195	0.88 (0.59-1.28)	1.18 (0.68-2.05)	890	0.94 (0.84-1.05)	0.99 (0.88-1.11)
>30	112	0.91 (0.60-1.44)	1.44 (0.77-2.70)	301	1.17 (1.01-1.36)^*	1.18 (1.00-1.38)^*
Cardiovascular disease	165	1.39 (1.00-1.94)	1.23 (0.38-4.01)
Psychiatric disease	137	1.56 (1.05-2.31)^*	1.43 (0.82-2.48)
Alcohol abuse	101	2.80 (1.89-4.15)^*^*	3.44 (2.01-5.89)^*^*	184	1.70 (1.44-2.02)^*^*	1.62 (1.37-1.93)^*^*
Diabetes	90	1.35 (0.91-2.03)	0.96 (0.52-1.75)
Cancer	59	1.45 (0.94-2.24)	1.73 (1.00-3.01)^*
FEV1% of predicted
>80	93	1.00	1.00
65-80	193	1.40 (0.52-3.76)	1.23 (0.38-4.00)
65-40	315	1.96 (0.78-4.92)	2.43 (0.84-7.06)
<40	136	3.38 (1.33-8.58)^*	5.26 (1.77-15.63)^*^*

^*p < 0.05, ^**p < 0.01, statistically significant values in bold.

†Patients with BMI <18 included (in COPD cohort N=11 in male smokers cohort N = 7).

Figure 1. Kaplan-Meier curves of overall survival during the follow up according to rs1051730 genotype (GG wild-type: solid line, GA heterozygote: dashed line, and AA homozygote: dotted line) in the COPD (left) and male smokers (right) cohorts. In COPD cohort the difference between the groups by log rank analysis is p = 0.03, in male smokers p < 0.01.

Table A1. Risk factors for having >40 pack-years

	COPD			Male smokers<./TSH>
	N	Crude OR (CI)	Adjusted OR (CI)	N	Crude OR (CI)	Adjusted OR (CI)
Age (per one year)	575	1.03 (1.01-1.06)^*^*	1.02 (1.00-1.05)	1911	1.02 (1.00 -1.04)	1.03 (1.01-1.05)^*^*
SNP, additive model
major homozygote	216	1.00	1.00	817	1.00	1.00
heterozygote	276	0.92 (0.55-1.53)	0.94 (0.63-1.39)	860	1.31 (1.08-1.59)^*^*	1.35 (1.10-1.65)^*^*
minor homozygote	83	0.86 (0.60-1.24)	1.07 (0.61-1.87)	234	1.37 (1.03-1.84)^*	1.41 (1.03-1.93)^*
smoking cessation during the follow-up	348	0.75 (0.55-1.01)^*	0.80 (0.54-1.18)	465	0.41 (0.33-0.51)^*^*	0.40 (0.32-0.50)^*^*
Alcohol abuse	101	1.52 (1.04-2.22)^*	1.65 (1.02-2.68)^*	184	1.85 (1.34-2.55)^*^*	1.76 (1.27-2.44)^*^*
Cancer	59	1.11 (0.69-1.78)	1.25 (0.68-2.30)
Men	372	1	1
Women	203	0.36 (0.26-0.50)^*^*	0.37 (0.24-0.55)^*^*
FEV1% of predicted
>80	77	1.00	1.00
65-80	133	1.20 (0.71-2.02)	1.37 (0.68-2.74)
65-40	258	1.68 (1.03-2.74)^*	1.53 (0.83-2.82)
>40	105	1.92 (1.11-3.33)^*	1.37 (0.71-2.64)

Model adjusted for BMI

^*p<0.05

^**p<0.01, statistically significant values in bold.

Table A2. Risk factors for having any type of cancer

	COPD
	N	Crude OR (CI)	Adjusted OR (CI)
Age (per one year)	575	1.07 (1.03-1.11)^*^*	1.10 (1.05-1.16)^*^*
SNP, additive model
major homozygote	216	1	1
heterozygote	276	1.76 (0.93-3.34)	1.70 (0.85-3.38)
minor homozygote	83	2.27 (1.01-5.07)^*	2.39 (1.00-5.67)^*
smoking cessation during the follow-up	348	0.82 (0.51-1.33)	1.38 (0.73-2.60)
Alcohol abuse	101	0.76 (0.39-1.47)	1.43 (0.64-3.16)
Pack-years>40 yrs	357	1.11 (0.69-1.78)	1.32 (0.72-2.42)
Men	372	1	1
Women	203	1.06 (0.65-1.73)	1.10 (0.57-2.11)
FEV1% of predicted
>80	77	1	1
65-80	133	0.76 (0.34-1.69)	0.59 (0.22-1.64)
65-40	258	0.78 (.037-1.61)	0.63 (0.26-1.56)
>40	105	1.20 (0.54-2.65)	0.79 (0.28-2.22)

^*p < 0.05,

^**p < 0.01, statistically significant values in bold.

Mohamed Hoesein FA, Wauters E, Janssens W, Groen HJ, Smolonska J, Wijmenga C, et al. Variants in the 15q24/25 locus associate with lung function decline in active smokers. PLoS One 2013; 8(1):e53219.

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