Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study

Imboden, Medea; Downs, Sara H; Senn, Oliver; Matyas, Gabor; Brändli, Otto; Russi, Erich W; Schindler, Christian; Ackermann-Liebrich, Ursula; Berger, Wolfgang; Probst-Hensch, Nicole M

doi:10.1186/1465-9921-8-2

Respiratory Research

Table 5 Adjusted* associations of GST genotypes† with excess annual decline in FEV1, FVC and FEF_25–75 in men and women, stratified by absence or presence of BHR at baseline or follow-up, the SAPALDIA Cohort.

From: Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study

BHR	Difference in mean annual change in lung function (ml/yr) ‡
negative	FEV1 (ml/yr)				FVC (ml/yr)				FEF25–75 (ml/yr)
	n	Coeff.	95%CI	p-value §	n	Coeff.	95%CI	p-value §	n	Coeff.	95%CI	p-value §
MEN
GSTT1 non-null	965	---		---	948	---		---	941	---		---
GSTT1 null	209	-4.4	-8.3, -0.5	0.027¶	208	-3.8	-9.0, 1.3	0.14	207	-4.2	-13.2, 4.8	0.36
GSTM1 non-null	560	---		---	550	---		---	546	---		---
GSTM1 null	614	-0.8	-3.8, 2.2	0.58	606	0.2	-3.7, 4.2	0.91	602	-3.4	-10.4, 3.5	0.33
GSTP1 105 Ile/Ile	557	---		---	547	---		---	542	---		---
GSTP1 105 Ile/Val	511	0.9	-4.1, 2.2	0.56	505	-0.7	-4.9, 3.4	0.95	503	-4.3	-11.6, 2.9	0.24
GSTP1 105 Val/Val	106	-0.6	-6.0, 4.9	0.84	104	-0.7	-7.9, 6.6	0.86	103	-3.7	-16.3, 9.0	0.57
GSTM1T1 both non-null	460	---		---	450	---		---	447	---		---
GSTM1T1 either null	605	-0.5	-3.7, 2.7	---	598	0.7	-3.5, 4.9	---	593	-3.2	-10.5, 4.1	---
GSTM1T1 both null	109	-6.4	-11.8, -1.0	0.062	108	-5.1	-12.3, 2.1	0.27	108	-8.0	-20.5, 4.5	0.41
	FEV1 (ml/yr)				FVC (ml/yr)				FEF25–75 (ml/yr)
	n	Coeff.	95%CI	p-value §	n	Coeff.	95%CI	p-value §	n	Coeff.	95%CI	p-value §
WOMEN
GSTT1 non-null	812	---		---	808	---		---	803	---		---
GSTT1 null	181	1.2	-1.8, 4.1	0.43	181	0.3	-3.9, 4.5	0.88	180	5.4	-2.0, 12.9	0.15
GSTM1 non-null	459	---		---	458	---		---	456	---		---
GSTM1 null	534	0.7	-1.6, 3.0	0.55	531	0.2	-3.0, 3.5	0.88	527	2.1	-3.7, 7.8	0.48
GSTP1 105 Ile/Ile	472	---		---	470	---		---	469	---		---
GSTP1 105 Ile/Val	430	-0.6	-2.4, 1.2	0.51	428	0.5	-2.9, 3.9	0.76	425	-5.6	-11.6, 0.5	0.072
GSTP1 105 Val/Val	91	-0.2	-3.3, 2.9	0.90	91	4.3	-1.6, 10.2	0.15	89	-3.6	-14.1, 6.9	0.50
GSTM1T1 both non-null	373	---		---	372	---		---	370	---		---
GSTM1T1 either null	525	-1.5	-3.9, 0.9	---	522	-1.1	-4.6, 2.3	---	519	4.4	-1.7, 10.6	---
GSTM1T1 both null	95	0.1	-4.1, 4.3	0.24	95	2.3	-3.6, 8.1	0.46	94	5.5	-5.0, 15.9	0.31
BHR	Difference in mean annual change in lung function (ml/yr) ‡
positive	FEV1 (ml/yr)				FVC (ml/yr)				FEF25–75 (ml/yr)
	n	Coeff.	95%CI	p-value §	n	Coeff.	95%CI	p-value §	n	Coeff.	95%CI	p-value §
MEN
GSTT1 non-null	276	---		---	267	---		---	265	---		---
GSTT1 null	51	-5.5	-14.7, 3.8	0.24	50	-5.5	-17.3, 6.3	0.36	50	-7.0	-24.2, 10.2	0.42
GSTM1 non-null	165	---		---	161	---		---	161	---		---
GSTM1 null	162	-8.2	-14.9, -1.5	0.017¶	156	-2.8	-11.4, 5.8	0.53	154	-12.4	-24.9, 0.08	0.051
GSTP1 105 Ile/Ile	142	---		---	139	---		---	137	---		---
GSTP1 105 Ile/Val	146	-0.7	-8.0, 6.6	0.84	139	-6.0	-15.3, 3.3	0.20	139	7.8	-5.8, 21.4	0.26
GSTP1 105 Val/Val	39	0.07	-10.8, 10.9	0.99	39	-2.8	-16.4, 10.9	0.69	39	-2.9	-22.8, 17.0	0.77
GSTM1T1 both non-null	139	---		---	136	---		---	136	---		---
GSTM1T1 either null	163	-6.1	-13.2, 1.0	---	156	-0.2	-9.3, 8.8	---	154	-11.6	-24.8, 1.6	---
GSTM1T1 both null	25	-17.3	-30.6, .4,1	0.024¶	25	-13.4	-30.2, 3.4	0.27	25	-20.2	-44.6, 4.3	0.12
*Among men: interaction Genotype BHR ††**
GSTT1*BHR				0.71				0.89				0.65
GSTM1*BHR				0.33				0.94				0.66
GSTP1*BHR				0.44				0.84				0.24
GSTM1T1*BHR				0.57				0.99				0.81
	FEV1 (ml/yr)				FVC (ml/yr)				FEF25–75 (ml/yr)
	n	Coeff.	95%CI	p-value §	n	Coeff.	95%CI	p-value §	n	Coeff.	95%CI	p-value §
WOMEN
GSTT1 non-null	437	---		---	428	---		---	423	---		---
GSTT1 null	101	-0.8	-5.8, 4.3	0.77	100	-1.1	-7.6, 5.4	0.74	99	0.8	-9.2, 10.9	0.87
GSTM1 non-null	251	---		---	246	---		---	244	---		---
GSTM1 null	287	0.6	-3.4, 4.6	0.76	282	1.0	-4.2, 6.1	0.72	278	0.9	-7.1, 8.8	0.83
GSTP1 105 Ile/Ile	250	---		---	246	---		---	243	---		---
GSTP1 105 Ile/Val	250	-2.4	-6.6, 1.7	0.24	244	-1.8	-7.1, 3.4	0.50	242	-5.5	-13.7, 2.7	0.19
GSTP1 105 Val/Val	38	2.2	-5.8, 10.2	0.59	38	5.3	-4.9, 15.6	0.31	37	-6.3	-22.2, 9.6	0.43
GSTM1T1 both non-null	206	---		---	202	---		---	200	---		---
GSTM1T1 either null	276	-1.5	-7.8, 2.8	---	270	-1.5	-7.0, 3.9	---	267	-2.8	-11.3, 5.7	---
GSTM1T1 both null	56	1.9	-5.0, 8.8	0.56	56	2	-6.8, 10.8	0.68	55	5.4	-8.4, 19.1	0.46
*Among women: interaction Genotype BHR ††**
GSTT1*BHR				0.25				0.23				0.52
GSTM1*BHR				0.85				0.67				0.47
GSTP1*BHR				0.77				0.87				0.35
GSTM1T1*BHR				0.41				0.85				0.24

* The effects of GST genotypes are adjusted for the respective baseline lung function parameter, smoking status at baseline and follow-up, pack-years smoked at baseline and during follow-up, height, weight change between surveys, study area, gas and dust exposure at baseline and education level.
† GSTM1 and GSTT1 genotypes were dichotomized into absence vs. presence of homozygous gene deletions (non-null vs. null). The effect of the GSTP1 genotype on lung function change was investigated in a co-dominant genetic model with the Ile/Ile genotype as the reference group. The combined GSTM1 /GSTT1 genotype (GSTM1T1) was coded as "presence of zero, one and two homozygous gene deletion polymorphisms" and included as ordinal variable in the linear regression model.
‡ Change in lung function parameter represented the difference between lung function parameter measured at follow-up [ml] and the one measured at baseline [ml] divided by the duration of follow-up period [yr]. Coefficient values below zero correspond to an excess decline in lung function [ml/yr] compared to the decline in the reference group and coefficient values above zero correspond to a less steep decline in lung function compared of the reference group.
§Uncorrected P-values for differences between categories.
¶Statistically significant (uncorrected P-value > 0.05).
†† Interaction between genotype and BHR was assessed by including interaction terms in the model.

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ISSN: 1465-993X

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