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United States Department of Agriculture

Agricultural Research Service


Location: Boston, Massachusetts

Title: Genetic variants at PSMD3 interact with dietary fat and carbohydrate to modulate insulin resistance

item Zheng, Ju-sheng
item Arnett, Donna
item Parnell, Laurence
item Lee, Yu-chi
item Ma, Yiyi
item Smith, Caren E.
item Richardson, Kris
item Li, Duo
item Ordovas, Jose M.
item Tucker, Katherine
item Lai, Chao Qiang
item Borecki, Ingrid B.

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/12/2012
Publication Date: 3/1/2013
Citation: Zheng, J., Arnett, D., Parnell, L.D., Lee, Y., Ma, Y., Smith, C., Richardson, K., Li, D., Ordovas, J., Tucker, K., Lai, C., Borecki, I. 2013. Genetic variants at PSMD3 interact with dietary fat and carbohydrate to modulate insulin resistance. Journal of Nutrition. 143(3):354-361.

Interpretive Summary: Insulin resistance (IR) is what happens when insulin becomes weak in lowering blood sugars, resulting in chronic diseases, such as type 2 diabetes, coronary heart disease, hypertension, inflammation, and aging. Some genes and diet act together with dietary fat to influence an individual’s risk of disease. Similar to what was found in the study, Lowering Drugs and Diet Network (GOLDN), our study shows that populations of different ethnic backgrounds are affected differently by the combination of genes and diet. Discovery of these genetic associations are important for diabetes prevention and may eventually help in the development of personalized nutrition.

Technical Abstract: Proteasome (prosome, macropain) 26S subunit, non-ATPase, 3 (PSMD3) encodes subunit 3 of the 26S proteasome, which is involved in regulating insulin signal transduction. We aimed to investigate the associations of PSMD3 variants with glucose-related traits and the interactions of those variants with dietary fat and carbohydrate for glucose-related traits in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study and to replicate the findings in the Boston Puerto Rican Health Study (BPRHS). Ten single nucleotide polymorphisms (SNPs) were selected covering 90% the genetic variations in/near PSMD3. Minor allele (C) carriers of rs4065321 had higher homeostasis model assessment of insulin resistance (HOMA-IR) than non-carriers in males of both GOLDN (P = 0.022) and BPRHS (P = 0.036). Minor allele (T) carriers of rs709592 had significantly higher HOMA-IR (P = 0.032) than C homozygotes in GOLDN, while the T allele carriers of rs709592 tended to have higher HOMA-IR (P = 0.078) than C homozygotes in BPRHS. In GOLDN, there were significant interactions between rs709592 and dietary carbohydrate on HOMA-IR (P = 0.049). Subjects carrying the T allele of rs709592 had higher HOMA-IR compared with non-carriers only with low carbohydrate intake (= 49.1% energy, P = 0.004). SNPs rs4065321 and rs709592 both significantly interacted with dietary monounsaturated fatty acids and carbohydrate for glucose levels in GOLDN. Our study suggests that PSMD3 variants associated with insulin resistance in populations of different ancestries, and that these relationships may also be modified by dietary factors.

Last Modified: 10/19/2017
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