INSIG2 variants, dietary patterns and metabolic risk in Samoa

Association of insulin-induced gene 2 (INSIG2) variants with obesity has been confirmed in several but not all follow-up studies. Differences in environmental factors across populations may mask some genetic associations and therefore gene-environment interactions should be explored. We hypothesized that the association between dietary patterns and components of the metabolic syndrome could be modified by INSIG2 variants.

We conducted a longitudinal study of adiposity and cardiovascular disease risk among 427 and 290 adults from Samoa and American Samoa (1990-1995). Principal component analysis on food items from a validated food frequency questionnaire was used to identify neotraditional and modern dietary patterns. We explored gene-dietary pattern interactions with the INSIG2 variants rs9308762 and rs7566605.

Results for American Samoans were mostly nonsignificant. In Samoa, the neotraditional dietary pattern was associated with lower triglycerides, body mass index (BMI), waist circumference, systolic and diastolic blood pressure and fasting glucose (all P-for-trend<0.05). The modern pattern was significantly associated with higher triglycerides, BMI, waist circumference and lower high-density lipoprotein-cholesterol (all P-for-trend<0.05). A significant interaction for triglycerides was found between the modern pattern and the rs9308762 polymorphism (P=0.04). Those from Samoa consuming the modern pattern have higher triglycerides if they are homozygous for the rs9308762 C allele.

The common INSIG2 variant rs9308762 was associated with poorer metabolic control and a greater sensitivity of trigylcerides to a modern dietary pattern. Environmental factors need to be taken into account when assessing genetic associations across and within populations.