Exploring how variants in this gene, which is involved in oxidative stress, might be associated with lung diseases, the authors examined several different patient cohorts (all white): 57 patients with chronic asthma, 68 with chronic obstructive pulmonary disease (COPD) associated with cigarette smoking, 144 lung cancer samples (94 with mild to moderate emphysema, 50 with no evidence of emphysema). These were compared to 203 control samples with no known history of lung disease. They examined two mutations in these samples: Tyr113His and His139Arg.
For this variant in the controls: YY: 91, YH: 99, HH: 13. In COPD, YY: 27, YH: 28, HH: 13. In emphysema, YY: 23, YH: 45, HH: 26. According to the authors, the HH genotypes are significantly different for COPD and emphysema with p-values of < 0.01 and < 0.0001 respectively.
The numbers for the controls deviate somewhat from Hardy-Weinberg equilibrium in the opposite direction (with an allele frequency of 9.5%, 19 out of 203 would be expected to be HH), exaggerating the significance of the number of HH homozygotes in disease groups. If the number of homozygotes in the controls had instead been 19, the number of homozygotes in the COPD group would be barely significant (p = 0.05). Although the numbers for the emphysema group still seem strong, it is unclear how well this group (based on tissue section diagnosis) relates to clinical symptoms of emphysema.