[ACT/AA polymorphism could duplicate the APOE*epsilon4-associated Alzheimer's disease risk].
OBJECTIVE
The association between the presence of the allele APOE*epsilon4 (apolipoprotein E) and sporadic Alzheimer disease (AD) has been long established. However, the possible influence of other genetic factors is still under debate. This study investigated the role of the a 1-antichymotrypsin (ACT) gene as a susceptibility factor for developing late-onset AD in the population of Navarra.


METHODS
The study group included 98 patients with late-onset AD and 188 control individuals 70-71 years of age. APOE*epsilon2,*epsilon3,*epsilon4 and ACT codon -17*A,*T polymorphisms were analyzed by PCR-RFLP. Statistical analyses were performed determining the chi-square test, using 2 x 2 contingency tables and logistic regression to calculate odds ratios.


RESULTS
APOE*epsilon4 allele frequency was significantly higher in AD patients than in controls (odds ratio [OR] = 3.02; 95% confidence interval [CI], 1.59-5.73; p < 0.001 in heterozygous carriers, and OR = 9.40; 95% CI, 1.84-64.43; p = 0.001 in homozygous individuals). We found no significant differences in the distribution of ACT polymorphisms between AD cases and controls. However, APOE*epsilon4 carriers had a 2.5-fold increased risk of developing AD in the presence of the ACT/AA genotype (OR = 10.13; 95% CI, 1.98-97.81; p < 0.001). The risk difference, however, did not reach statistical significance (p = 0.271).


CONCLUSIONS
APOE*epsilon4 heterozygous and homozygous carriers have a 3 and 9 times higher risk, respectively, of developing AD. We could not demonstrate an effect of ACT polymorphisms as a independent risk factor for this disease; however, the ACT/AA genotype seems to act as an additional susceptibility factor, duplicating the APOE*epsilon4-associated AD risk.
Servicio de Genética Médica, Hospital Virgen del Camino, Pamplona, Spain.
Blanca
B
Hernández-Charro
Sira
S
Moreno
Alberto
A
Valiente
José María
JM
Manubens
María Dolores
MD
Villar
María Antonia
MA
Ramos-Arroyo
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D000514:alpha 1-Antichymotrypsin / Q000235:genetics*
D001057:Apolipoproteins E; D000514:alpha 1-Antichymotrypsin