Notably, HHIP haploinsufficiency has been found to result in increased age-related emphysema in a mouse model [41], and variation in the CHRNA3/CHRNA5 locus is associated with nicotine dependence and lung function, suggesting its role in COPD is related to tobacco use and/or metabolism [42]. This evidence concerns the gene CHRNA5 and chronic obstructive pulmonary disease.