Genetic variation in angiotensin converting-enzyme affects the white matter integrity and cognitive function of amnestic mild cognitive impairment patients

Angiotensin-converting enzyme (ACE) gene has been implicated in amnestic mild cognitive impairment (aMCI). Most human genetic studies have focused on ACE insertion (I)/deletion (D) polymorphism and yielded conflicting results. In this work, we evaluated the relationships between cognitive function, serum ACE level, brain white matter (WM) integrity, and ACE I/D polymorphism in 48 patients with aMCI and 36 well matched control subjects from south China. In aMCI patients, D allele frequency was higher (D/I ratio = 0.51:0.49) than that of the control subjects (D/I ratio = 0.43:0.57); however, the difference was not statistically significant (p > 0.05). The D carriers in aMCI subjects performed significantly poorer on auditory-verbal learning test (AVLT) -delayed recall than the I homozygous group (p = 0.035). These carriers had higher serum ACE level than the I homozygous carriers of aMCI (p = 0.037). In the aMCI group, D carriers showed significantly lower fractional anisotropy (FA) values in the left middle frontal gyrus, left anterior cingulate, right gyrus parahippocampalis, right inferior parietal lobule, and bilateral anterior central gyrus than the I homozygotes carriers. However, no significant difference was observed in FA values between I homozygotes and D carriers in the control subjects. The ACE D allele in aMCI patients may increase the risk of cognitive impairment. A high serum ACE level possibly plays an important role in the incidence of aMCI.