Explore the role of CR1 genetic variants in late-onset Alzheimer's disease susceptibility.

Background: Complement component (3b/4b) receptor 1 (CR1) is an interesting candidate gene which has a close connection with Alzheimer's disease, and its polymorphisms have been reported to link to the late-onset Alzheimer's disease (LOAD) susceptibility. However, the findings of these related studies are inconsistent. Objective To explore the effect of CR1 genetic variants in LOAD susceptibility. MethodsWe searched relevant studies for the period up to 1 November 2020. And odds ratios (ORs) and their 95% confidence intervals (CIs) were utilized to assess the strength of the association. In addition, we carried out a case-control association study to assess their genetic association.

Results: Finally, a total of 30 articles with 30108 LOAD cases and 37895 controls were included. Significant allele frequency between LOAD patients and controls was observed in rs3818361 and rs6656401 (rs3818361, T vs. C: OR,1.18; 95% CI, 1.13-1.23; rs6656401, A vs. G: OR, 1.23; 95% CI, 1.10-1.36). Moreover, these results remain significant in subgroup of rs3818361 in Asia or America (OR,1.26; 95% CI,1.06-1.45; OR, 1.18; 95% CI, 1.13-1.24, respectively) and rs6656401 in Europe (OR = 1.26; 95% CI, 1.09-1.42). In addition, the two single nucleotide polymorphisms were proved to significantly increase LOAD risk in the overall population under the dominant model (OR = 1.12; 95% CI, 1.02-1.21; OR = 1.18, 95% CI, 1.15-1.22, respectively). Our case-control study showed that the distribution of rs6656401 genotype was significant (P = 0.000; OR, 6.889; 95% CI, 2.709-17.520), suggesting the A allele of rs6656401 is the risk allele.

Conclusion: These available data indicate that rs6656401 in CR1 is significant to increase LOAD risk.