Background: Both in vitro and in vivo, overexpression of the sortilin-related VPS10 domain containing receptor 1 (SORCS1) protein lowers amyloid-β generation. Recent studies have shown that SORCS1 variations in intron 1 are associated with sporadic Alzheimer's disease (SAD), but the results remain inconsistent.
Methods: In order to clarify the role of the SORCS1 gene in southern Han Chinese, we genotyped eight single nucleotide polymorphisms (SNP) of SORCS1 in 128 SAD patients and 92 healthy controls.
Results: By dividing patients and controls according to apolipoprotein status, sex and whether they had type 2 diabetes mellitus, we found that rs7907690 C allele frequencies were significantly higher in the Alzheimer's disease (AD) patients with type 2 diabetes mellitus than in the controls (P= 0.041). Also, the rs600879 GG genotype and G allele worked as protective factors of SAD in women (GG genotype, P= 0.007; G allele, P= 0.009). In multilocus analysis, the frequency of an eight-single nucleotide polymorphism rs601883/rs7907690/rs600879/rs17277986/rs2900717/rs10884399/rs11193170/rs4918280 CCGGACGG haplotype was significantly higher in AD patients (6.3%), especially in female AD patients (9.5%), than in the controls (0.5%) (P= 0.003; P= 0.0002). However, the CTGGACGG haplotype was significantly lower in AD patients (9.3%) than in controls (20.3%) (P= 0.001). The association remained significant even after Bonferroni correction for the number of haplotypes.
Conclusion: This study provides evidence that variations in the SORCS1 gene influence susceptibility to SAD in southern Han Chinese. The genetic link between AD and SORCS1 gene variations are influenced by ethnic background, sex and whether an individual has type 2 diabetes mellitus.