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Interaction Between the Ratio of Polyunsaturated Fat and Saturated Fat Intake and Peroxisome Proliferator‐Activated Receptor‐γ Coactivator 1‐α ( PPARGC1A ) rs4235308 Polymorphism in Relation to the Risk of Type 2 Diabetes in Cuban American Population
Author(s) -
Xu Ling,
Cheema Amanpreet,
Zarini Gustavo G.,
Li Tan,
Huffman Fatma G.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.644.16
Subject(s) - ppargc1a , type 2 diabetes , endocrinology , medicine , coactivator , biology , chemistry , diabetes mellitus , genetics , gene , transcription factor
Background Results from multiline studies suggested that oxidative stress might be the underlying cause of the development of insulin resistance, β‐cell dysfunction, impaired glucose tolerance and type 2 diabetes (T2D). The importance of the peroxisome proliferator‐activated receptor‐gamma, coactivator 1 ( PPARGC1A ) in mitochondrial biogenesis and regulation of oxidative stress has been extensively investigated. Association of PPARGC1A variants with T2D has been confirmed in several studies. Differences in environmental factors, particularly dietary factors influencing oxidative stress balance, may mask some genetic association. We hypothesized that the association of a common variant (SNP rs4235308) in PPARGC1A gene may be altered by the ratio of polyunsaturated to saturated fats (P/S fat ratio) in the diet. Subjects/Methods We genotyped rs4235308 polymorphism in the PPARGC1A gene from 315 Cuban Americans (164 without T2D/151 with T2D) using ABI TaqMan assays. Logistic regression method was used to assess the association between rs4235308 genotypes in an additive model and the risk of T2D. Interaction was tested by including the product of genotype*P/S fat ratio in the model. Results There was no significance between rs4235308 polymorphism and the risk of T2D when we didn't include the P/S fat ratio in the model. After including the P/S fat ratio and the interaction term in the model, a strong interaction was evident between P/S fat ratio and rs4235308 polymorphism for the risk of T2D (P=0.010) after adjusting for body mass index (BMI), age, gender, physical activity and calorie intake. SNP rs4235308 (OR=0.57, P=0.027) showed a protective association with T2D for the subgroup who has a lower P/S fat ratio (P/S fat ratio < median (0.456)) while there were no significant results when the same analysis was conducted in the subgroup that had a higher P/S fat ratio (P/S fat ratio ≥ median). In addition, we found that the P/S fat ratio was negatively associated with serum HDL‐cholesterol level in T2D patients (P=0.008) after adjustment of BMI, age, gender, physical activity and calorie intake. Further analysis on this association stratified by genotyping status (C allele carrier vs. non‐carrier) showed that the negative association between serum HDL‐cholesterol and the P/S fat ratio in patients with T2D was only significant in non‐carrier (P=0.021). Conclusion The common PPARGC1 A rs4235308 variant was associated with decreased risk of T2D in Cuban American when dietary P/S fat ratio was low. Dietary factors need to be taken into consideration when investigating genetic associations with T2D within populations. Support or Funding Information Funding for this research was provided through an NIH/NIDDK sponsored grant # SC1DK083060