Table 3.
GST polymorphisms and their contribution to GST function, and the risk of the variant allele (compared to wild-type allele) on the chronic lung diseases asthma and COPD.
| Genetic variant | Function | Asthma | COPD |
|---|---|---|---|
| GSTA1* −69C/T, rs3957357 | Promotor variant, reduced protein expression [70] | Increased risk in adults [201,202]; Associated with allergies [202] | No data |
| GSTM1 G > C rs412543 GSTM1 null |
Promotor variant 16 kb deletion – loss of protein expression [78,79] |
Increased risk in children [104] Increased risk to (atopic) children & adults [204,205], especially in combination with exposure to tobacco smoke [164], meta-analysis [43,84,203]; no association [206,219,220]; increased risk but not when only restricted to larger studies [203] |
Increased risk, meta-analysis [83,234,238,240]; no association [44] |
| GSTO1 Ala140Asp (A140D), 419C > A, rs4925 GSTO1-E155del GSTO2 Asn142Asp (N142D), 424A > G, rs156697 |
Coding sequence variant with variable effects on activity [85,86,88,95] Coding sequence variant with reduced expression [86] |
No association [201] No association [201] Increased risk in adults [201,202] |
Increased risk as haplotype with rs156697 [227] Increased risk [227] |
| GSTP Ile105Val (L105V), 313A > G, rs1695 GSTP1 Ala114Val (A114V), 341C > T, rs1138272 |
Coding sequence variant with decreased activity [45] Coding sequence variant with not known activity |
Decreased risk [204,205,213]; no association [40,216,220]; increased risk to (atopic) asthma in children & adults [46,116]; increased in combination with environmental exposure [214,215]; No significant association in meta-analysis [219] Increased risk at young age [214] No association in children [216] |
Decreased risk [232,233]; increased risk [229] – in particular in α1-antitrypsin deficiency [230] – meta-analysis [236]. No association in meta-analysis [47,235] |
| GSTT1 null | Whole or partial ~ 54 kb deletion - loss of protein expression [41,42] | Increased risk to asthma attack in children [220], increased risk to atopic asthma [204], meta-analysis [43,84,219]; no association [206]; increased risk but not when only restricted to larger studies [203] | Increased risk [44], especially for emphysema [237], meta-analysis [83] |
Table describes different GST polymorphisms that have been associated with asthma or COPD in the literature. COPD: Chronic Obstructive Pulmonary Disease; GST: Glutathione S-transferase.