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 3 Adjusted* associations of GST genotypes† with excess annual decline in FEV1, FVC and FEF_25–75 stratified by sex, the SAPALDIA Cohort.

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

	Difference in mean annual change in lung function (ml/yr) ‡
	FEV1 (ml/yr)				FVC (ml/yr)				FEF_25–75 (ml/yr)
	n	Coeff.	95%CI	p-value §	n	Coeff.	95%CI	p-value §	n	Coeff.	95%CI	p-value §
MEN
GSTT1 non-null	1853	---		---	1806	---		---	1787	---		---
GSTT1 null	378	-5.3	-8.4, -2.1	0.001¶**	371	-5.2	-7.4, -1.3	0.17	366	-5.0	-11.7, 1.8	0.15
GSTM1 non-null	1060	---		---	1040	---		---	1030	---		---
GSTM1 null	1171	-2.1	-4.5, 0.3	0.081	1137	-0.8	-4.0, 2.5	0.65	1123	-4.1	-9.2, 0.9	0.11
GSTP1 105 Ile/Ile	1057	---		---	1037	---		---	1025	---		---
GSTP1 105 Ile/Val	957	0.09	-2.4, 2.6	0.94	929	-0.1	-3.5, 3.3	0.95	919	-2.7	-8.0, 2.6	0.32
GSTP1 105 Val/Val	217	-2.5	-6.6, 1.7	0.25	211	-3.2	-9.0, 2.5	0.27	209	-7.3	-16.1, 1.6	0.11
GSTM1T1 both non-null	885	---		---	866	---		---	860	---		---
GSTM1T1 either null	1143	-1.8	-4.3, 0.7	---	1114	0.9	-2.5, 4.4	---	1097	-5.1	-10.5, 0.2	---
GSTM1T1 both null	203	-8.3	-12.6, -3.9	<0.001¶**	197	-6.5	-12.5, -0.5	0.045¶	196	-7.8	-17.0, 1.5	0.094
*GSTT1* * *GSTM1* Interaction				0.30				0.042¶				0.55
WOMEN
GSTT1 non-null	1989	---		---	1953	---		---	1920	---		---
GSTT1 null	466	-0.3	-2.5, 1.8	0.76	462	-1.6	-4.5, 1.3	0.28	455	3.4	-1.5, 8.3	0.18
GSTM1 non-null	1149	---		---	1131	---		---	1115	---		---
GSTM1 null	1306	0.5	-1.2, 2.2	0.54	1284	1.1	-1.2, 3.4	0.36	1260	-0.8	-4.7, 3.1	0.69
GSTP1 105 Ile/Ile	1162	---		---	1142	---		---	1126	---		---
GSTP1 105 Ile/Val	1068	-0.6	-2.4, 1.2	0.51	1050	0.6	-1.8, 3.0	0.64	1030	-3.0	-7.0, 1.1	0.15
GSTP1 105 Val/Val	225	-0.2	-3.3, 2.9	0.90	223	1.5	-2.6, 5.6	0.48	219	0.5	-6.5, 7.5	0.88
GSTM1T1 both non-null	931	---		---	915	---		---	902	---		---
GSTM1T1 either null	1276	-0.9	-2.7, 1.0	---	1254	-1.1	-3.5, 1.4	---	1231	-0.6	-4.8, 3.5	---
GSTM1T1 both null	248	1.6	-1.5, 4.6	0.24	246	1.3	-2.7, 5.4	0.42	242	3.2	-3.6, 10.0	0.53
*GSTT1* * *GSTM1* Interaction				0.026¶				0.025¶				0.66
*Sex Genotype Interaction**††
sex*GSTT1				0.010¶				0.56				0.043¶
sex*GSTM1				0.028¶				0.23				0.19
sex*GSTP1				0.50				0.39				0.40
sex*GSTT1M1				<0.001¶				0.015¶				0.08¶

* 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. Bonferroni corrected significance level for multiple comparisons: P < 0.0017.
¶Statisically significant (uncorrected P-value > 0.05). ** Statistically significant after Bonferoni-correction (P-value > 0.0017)
†† Interaction between genotype and gender was assessed by including interaction terms in the model.

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