Perilipin gene variation determines higher susceptibility to insulin resistance in Asian women when consuming a high-saturated fat, low-carbohydrate diet.
OBJECTIVE
To investigate the association between genetic variation in the adipocyte protein perilipin (PLIN) and insulin resistance in an Asian population as well as to examine their modulation by macronutrient intake.


METHODS
A nationally representative sample (Chinese, Malays, and Indians) was selected in the Singapore National Health Survey following the World Health Organization-recommended model for field surveys of diabetes. A total of 1,909 men and 2,198 women (aged 18-69 years) were studied. Genetic (PLIN 11482G-->A and 14995A-->T), lifestyle, clinical, and biochemical data were obtained. Homeostasis model assessment of insulin resistance (HOMA-IR) was used to evaluate insulin resistance. Diet was measured by a validated food frequency questionnaire in one of every two subjects.


RESULTS
We did not find a significant between-genotype difference in insulin resistance measures. However, in women we found statistically significant gene-diet interactions (recessive model) between PLIN 11482G-->A/14995A-->T polymorphisms (in high linkage disequilibrium) and saturated fatty acids (SFAs; P = 0.003/0.005) and carbohydrate (P = 0.004/0.012) in determining HOMA-IR. These interactions were in opposite directions and were more significant for 11482G-->A, considered the tag polymorphism. Thus, women in the highest SFA tertile (11.8-19%) had higher HOMA-IR (48% increase; P trend = 0.006) than women in the lowest (3.1-9.4%) only if they were homozygotes for the PLIN minor allele. Conversely, HOMA-IR decreased (-24%; P trend = 0.046) as carbohydrate intake increased. These effects were stronger when SFAs and carbohydrate were combined as an SFA-to-carbohydrate ratio. Moreover, this gene-diet interaction was homogeneously found across the three ethnic groups.


CONCLUSIONS
PLIN 11482G-->A/14995A-->T polymorphisms modulate the association between SFAs/carbohydrate in diet and insulin resistance in Asian women.
Corella
Dolores
D
Nutrition and Genomics Laboratory, JM-USDA-HNRCA at Tufts University, 711 Washington St., Boston, MA 02111, USA. jose.ordovas@tufts.edu
Qi
Lu
L
Tai
E Shyong
ES
Deurenberg-Yap
Mabel
M
Tan
Chee Eng
CE
Chew
Suok Kai
SK
Ordovas
Jose M
JM
D044466:Asian People; D002352:Carrier Proteins; D050528:Diet, Carbohydrate-Restricted; D004041:Dietary Fats; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012846:Singapore
D002352:Carrier Proteins; D004041:Dietary Fats; D000070778:Perilipin-1; D010750:Phosphoproteins