rs429358

rs429358 is a single nucleotide polymorphism in the apolipoprotein E (APOE) gene on chromosome 19. It involves a cytosine to thymine substitution that changes the codon for amino acid 112 from cysteine to arginine. Specifically, the C allele encodes cysteine at position 112, while the T allele encodes arginine.

This SNP does not act alone. Together with rs7412, another APOE variant, rs429358 helps define the three major APOE alleles: ε2, ε3, and ε4. The ε3 allele corresponds to rs429358 C and rs7412 C; ε4 corresponds to rs429358 T and rs7412 C; ε2 corresponds to rs429358 C and rs7412 T. These haplotypes influence lipid transport and metabolism and are a major source of variation in human APOE function.

Clinically, the APOE ε4 allele is associated with an increased lifetime risk of late-onset Alzheimer's disease and higher atherosclerotic cardiovascular risk compared with other APOE alleles. The ε3 allele is the most common and is generally considered neutral with respect to AD risk. The ε2 allele is sometimes reported as protective against Alzheimer's disease but can be linked to elevated risk of type III hyperlipoproteinemia in certain contexts. However, possessing ε4 does not guarantee disease, and many carriers never develop these conditions; risk is modulated by age, environment, and other genetic factors.

rs429358 has been extensively studied in genetic research and is frequently included in studies of APOE genotype. Its interpretation requires context, as APOE-related risk is probabilistic rather than deterministic.