Heterozygous Genotype rs17580 AT (PiS) in SERPINA1 is Associated with COPD Secondary to Biomass-Burning and Tobacco Smoking: A Case–Control and Populational Study

Figures & data

Table 1 Description of Demographic Variables of the COPD Patients and Expositional Comparison Groups

Variable	COPD-S n=399	SWOC n=1106	p-value	COPD-BS n=98	BBES n=275	p-value
Age, years	66 (42–87)	56 (40–90)	<0.001*	70 (54–97)	64 (42–90)	<0.001*
Sex, (%)
Male	284 (71.0)	793 (71.69)	0.418**	8 (8.1)	0	<0.01**
Female	116 (29.0)	313 (28.31)		90 (91.9)	98 (100)
Smoking status
Years of smoking	40 (1–68)	30 (3–65)	<0.001*	NA	NA
Cigarettes per day	20 (1–80)	18 (1–80)	<0.001*	NA	NA
Packs-year history	39 (6.3–200)	26 (5.2–168)	<0.001*	NA	NA
Exposure to biomass-burning smoke
Exposure years	NA	NA		30 (12–80)	15 (14–76)	<0.001*
Hours/day	NA	NA		8 (1–16)	6 (1–14)	<0.001*
Exposure index	NA	NA		180 (16–800)	86 (8–536)	<0.001*
Lung function post-bronchodilator
FVC % predicted	85 (10–185)	96 (29–156)	<0.001*	87 (41–178)	92 (41–128)	<0.001*
FEV1% predicted	58 (14–160)	99 (37–160)	<0.001*	59 (14–130)	93 (31–129)	<0.001*
FEV1/FVC (%)	54 (18–89)	83 (70–111)	<0.001*	54 (29–69)	94 (70–119)	<0.001*
GOLD, %
I	19.5	NA		36.7	NA
II	41.0	NA		35.7	NA
III	29.5	NA		25.5	NA
IV	9.8	NA		2.1	NA
Regional distribution, %
North	2.5	1.5	0.165**	2.04	1.02	1.0**
Central	84.0	87.4	0.105**	67.35	75.51	0.268**
South	13.5	11.1	0.205**	30.61	23.46	0.334**

Notes: The p-value determined by the Mann–Whitney U-test. *The p-value determined by the χ squared test. **Showing median, minimum, and maximum values.

Abbreviations: COPD-S, COPD patients secondary to tobacco smoking; SWOC, smokers without COPD; COPD-BS, COPD patients secondary to biomass-burning smoke exposure; BBES, biomass-burning exposed subjects without COPD.

Table 2 Genotype and Allele Frequency Comparisons in COPD Patient Groups and Smokers/Biomass-Burning Smoke-Exposed Subjects

SNP	COPD-S		SWOC		p-value*	COPD-BS		BBES		p-value*
	n=399	%	n=1106	%		n=98	%	n=275	%
rs28929474 (PiZ)
Dominant model
GG	391	97.99	1095	99.01	0.09885	97	98.98	275	100.0	0.13135
GA+AA	8	2.01	11	0.99		1	1.02	0	0
Allele
G	790	99.00	2200	99.46	0.13195	195	99.43	550	100.0	0.12120
A	8	1.00	12	0.54		1	0.57	0	0
rs17580 (PiS)
Dominant model
AA	350	87.72	1037	93.76	0.00009	87	88.78	272	98.91	0.00002
AT+TT	49	12.28	69	6.24		11	11.22	3	1.09
Allele
A	749	93.86	2142	96.84	0.00006	185	94.39	547	99.45	0.00002
T	49	6.14	70	3.16		11	5.61	3	0.55

Note: *p-value after Bonferroni correction.

Abbreviations: COPD-S, COPD patients secondary to tobacco smoking; SWOC, smokers without COPD; COPD-BS, COPD patients secondary to biomass-burning smoke exposure; BBES, biomass-burning exposed subjects without COPD.

Table 3 Ancestral Contribution of the Mexican-Mestizo Regions Under the Study

Region	Contribution (%)
	Caucasian	Amerindian
North	54.7	45.3
Central	46.9	53.1
Southeast	42.5	57.5
Mexican Mestizo (average)	48.1	51.9

Table 4 Genotype and Allele Frequencies (%) in Mestizo and Amerindian Populations of Mexico

SNP	Mestizo				Amerindian
	North n=166	Central n=1512	Southeast n=274		Otomi n=84	Maya n=38	Mazahua n=280
rs28929474 (PiZ)
Genotype
GG	94.6	97.8	98.5		100	94.7	100
GA	5.4	2.2	1.5		0	5.3	0
AA	0	0	0		0	0	0
Allele
G	97.3	98.9	99.3		100	97.4	100
A	2.7	1.1	0.7		0	2.6	0
rs17580 (PiS)
Genotype
AA	88.6	95.5	96.7		95.2	94.7	98.9
AT	11.4	4.4	3.3		4.7	5.3	1.1
TT	0	0.07	0		0	0	0
Allele
A	94.3	97.8	98.4		97.6	97.4	99.5
T	5.7	2.2	1.6		2.4	2.6	0.5

Note: All values are expressed in percentages.

Figure 1 Population structures of the Mexican Mestizo groups and the reference populations (CEU and AME) The arrow indicates an individual with both risk genotypes (AT and GA for PiS and PiZ, respectively) whose Caucasian contribution reaches 0.935 and only 0.065 for Native American ancestry.