APOA2

Risk Description

This SNP is one of those interesting variants where the environment in which it is expressed can modulate which direction of effect it has.

The ‘G’ allele of the SNP rs5082 in the APOA2 gene is associated with increased levels of  LDLc and an altered LDL:HDL ratio following saturated fat intake and excessive carbohydrate intake, which is shown by the associated increased risks of cardiovascular disease and type 2 diabetes ^2,3. Interestingly when saturated fat intake was reduced carriers of the ‘G’ allele displayed significantly lowered total cholesterol, triglyceride, Cholesterol/HDL-c ratio and non-HDL cholesterol than A allele carriers, coupled with an almost 50% reduction in risk of developing cardiovascular disease⁴.

In contrast, we can view the ‘A’ allele as the default allele. In those following a traditional carbohydrate and saturated fat-rich western diet, the ‘A’ allele will present a lower risk than the ‘G’ allele. However, where a more regulated diet is followed, lower in carbohydrate and saturated fat, then the ‘A’ allele can actually be considered more risky.

It has been demonstrated that the ‘G’ allele is associated with reduced expression of APOA2, however, the science linking this reduced expression with altered risk is poorly understood. One study suggested that the effect may be mediated by changes in HDL particle count and type in those carrying the ‘G’ allele. Or that there is a reduction in plasma LDL and triglyceride particle count following a low carb/low saturated fat meal with this beneficial effect being masked when a high carb/high saturated fat diet is followed. However, this effect has not been replicated in other studies^,5.