Rs705381

rs705381, also known as -161C/T and -162A/G, is a SNP in the upstream promoter region of the PON1 gene. (The assumption of equivalence between these names is based on the results of searching for rs705381 in the Variant Name Mapper.)

In a study of 101 mostly Caucasian patients prescribed the atypical antipsychotic risperidone, carriers of a rs705381(C) allele were less likely to gain significant weight compared to rs705381(T;T) carriers, as assessed by physiogenomic analysis of corresponding weight profiles. Two other SNPs, rs8179183 and rs6837793, were also significantly associated with weight profiles in these patients.

In a study of 461 participants in the HERITAGE cohort (172 African-American, 289 Caucasian), the combination of rs705381 with "PON-126" (RS ID unknown) were found to significantly contribute to trait-anxiety scores. The authors also cite another paper,, which found that this SNP accounts for 2.4% of the variation in PON1 expression. Which allele correlates with increased trait-anxiety scores and/or reduced PON1 expression is unclear.

HapMap frequencies for this SNP seem dubious. They list rs705381(T;T) as being at or near 100% for the population groups reported by SNPedia. However, the raw data at HapMap for this SNP are largely no-call (e.g. CEU: NN=87, TT=82, CT=3). The other diversity studies listed at dbSNP show C as the more common allele (e.g. AFD_AFR_PANEL: CC=47.8%, CT=39.1%, TT=13.0%). Anecdotal data submitted by participants at 23andme also show C as being more common (CC=4, CT=1, TT=2). The diversity data have therefore been removed until these discrepancies can be resolved.

A common haplotype within the PON1 promoter region is associated with sporadic ALS.

A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS.

Association analysis of PON2 genetic variants with serum paraoxonase activity and systemic lupus erythematosus.