Klotho gene promoter polymorphism and cognitive impairment

Aim:   To study the association between the klotho gene polymorphism and cognitive impairment in community-living men and women.
Methods:   The subjects consisted of 2234 community-living Japanese men and women aged 40–79 years. The klotho gene promoter polymorphism G- 395 A was identified and cognitive function was assessed using the Japanese Wechsler Adult Intelligence Scales – Revised Short Forms ( JWAIS-R SF) and Mini-Mental State Examination (MMSE). Brain infarction and atrophy were assessed by brain magnetic resonance imaging (MRI). The differences in cognitive function, infarction and atrophy were compared between the GG type and GA/AA type of the klotho gene G- 395 A polymorphism.
Results:   The distribution of the klotho gene G- 395 A polymorphism was GG 1639 (73.4%), GA 539 (24.1%), and AA 56 (2.5%). There was no significant difference in intelligence quotient (IQ) between the GG type and GA/AA type in the subjects aged 40–59 years. However, the IQ level was significantly different in terms of the klotho genotype for subjects aged 60–79 years ( P  = 0.004). The mean and SE of IQ levels of the subjects with the GG type and the GA/AA type at nucleotide ?395 were 99.8 ± 0.5 and 102.6 ± 0.8, respectively. There were also significant differences in three subtests of JWAIS-R SF – Information, Similarities, and Picture Completion – for subjects aged 60–79 years. Also, the MMSE score was slightly lower for the GG type than for the GA/AA type ( P  = 0.099). However, there were no differences in the findings of brain MRI.
Conclusion:   There were statistically significant differences in cognitive function for klotho gene promoter polymorphism G- 395 A only in subjects aged 60 or over. This polymorphism may be associated with age-related cognitive impairment.