FERMT2 rs17125944 polymorphism with Alzheimer's disease risk: a replication and meta-analysis

Abstract

A recent meta-analysis of genome-wide association studies (GWAS) in population of Caucasian identified a single nucleotide polymorphism (SNP) rs17125944 in the FERMT2 gene as a new susceptibility locus for late-onset Alzheimer's disease (LOAD). In order to validate the association of the rs17125944 polymorphism with LOAD risk in the northern Han Chinese, we recruited a case–control study of 2338 Han Chinese subjects (984 cases and 1354 age- and gender-matched controls). Our results demonstrated that there was no significant association between the rs17125944 polymorphism and LOAD (genotype: P = 0.953; allele: P = 0.975). Furthermore, no significant differences were observed in alleles and genotypes distribution after stratification by apolipoprotein E (APOE) ε4 and multivariate logistic regression analysis. We also performed a meta-analysis in 81908 individuals. The meta-analysis showed that the C allele is the risk factor for LOAD in Caucasian group (OR = 1.15, 95 % CI = 1.10–1.20) and combined population (OR = 1.13, 95 % CI = 1.08–1.19). While in Chinese population, the C allele is not associated with increased risk of LOAD (OR = 1.07, 95 % CI = 0.89–1.28). In conclusion, our study showed that the rs17125944 polymorphism in FERMT2 gene might not be association with LOAD in northern Han Chinese population.

Genetic Association of FERMT2, HLA-DRB1, CD2AP, and PTK2B Polymorphisms With Alzheimer’s Disease Risk in the Southern Chinese Population

“…A meta-analysis of GWAS in individuals of European ancestry identified rs17125944 of FERMT2 as a risk factor for LOAD, even though this was inconsistent in different ethnic groups (Lambert et al, 2013). Zhang et al (2016) could not corroborate this association in the northern Han Chinese population. No studies have yet been conducted to assess the relationship between SNP rs17125924 within the FERMT2 gene and AD susceptibility in the Asian population.…”

BIN1 rs744373 variant shows different association with Alzheimer’s disease in Caucasian and Asian populations

“…Besides the most consistent genetic risk factor ApoE for Sporadic AD, some studies have also reported many genetic risk factors that appear distinct AD susceptibility between Caucasian and East Asian populations. For instance, following genes were proven to be only associated with AD risk in Caucasian populations but not in East Asian populations: Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) [44, 45], Solute Carrier Family 24 Member 4 (SLC24A4) [46], NME/NM23 Family Member 8 (NME8) [47], GRB2 Associated Binding Protein 2 (GAB2) [48], Myocyte Enhancer Factor 2C (MEF2C) [49], Inositol Polyphosphate-5-Phosphatase D (INPP5D) [50], CLU [51], ABCA7, CD2AP, and EPHA1 [25], Fermitin Family Member 2 (FERMT2) [52]. Hence, the complex difference among different ethnicities and races probably cause the genetic heterogeneity of AD between Caucasians and East Asians.…”

Genetic and Expression Analysis of COPI Genes and Alzheimer’s Disease Susceptibility

“…Large-scale genome-wide association studies (GWASs) have identified several novel genetic risk loci in European population, and candidate gene studies have replicated these findings in other populations (Liu et al, 2012; Liu et al, 2013b; Liu et al, 2013c; Liu et al, 2013d; Liu et al, 2014a; Liu et al, 2014b; Liu et al, 2014c; Chen et al, 2015; Li et al, 2015; Shen et al, 2015; Zhang et al, 2015; Chang et al, 2016; Li et al, 2016; Liu and Jiang, 2016; Liu et al, 2016; Ma et al, 2016; Tan et al, 2016; Zhang et al, 2016b). Whole-genome sequencing has highlighted the role of TREM2 in AD (Jiang et al, 2016; Zhang et al, 2016a; Ulland and Colonna, 2018). However, these AD susceptibility loci could only explain 28.57% AD genetic risk (Cuyvers and Sleegers, 2016).…”