title: Genetic variants at PSMD3 interact with dietary fat and carbohydrate to modulate insulin resistance.
abstract: PSMD3 encodes subunit 3 of the 26S proteasome, which is involved in regulating insulin signal transduction, and dietary factors could potentially regulate the function of this gene. 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 or near PSMD3. Minor allele (C) carriers of rs4065321 had higher homeostasis model assessment of insulin resistance (HOMA-IR) than noncarriers in males of both the 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 the GOLDN, whereas the T allele carriers of rs709592 tended to have higher HOMA-IR (P = 0.08) than C homozygotes in the BPRHS. In the GOLDN, there was an interaction between rs709592 and dietary carbohydrate on HOMA-IR (P = 0.049). Subjects carrying the T allele of rs709592 had higher HOMA-IR compared only with noncarriers with low carbohydrate intake (≤49.1% energy; P = 0.004). SNPs rs4065321 and rs709592 both significantly interacted with dietary MUFAs and carbohydrate on glucose concentrations in the GOLDN. Our study suggests that PSMD3 variants are associated with insulin resistance in populations of different ancestries and that these relationships may also be modified by dietary factors.
authors.affiliation: Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China.
authors.forename: Ju-Sheng
authors.initials: JS
authors.lastname: Zheng
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Parnell
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Lee
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Ma
authors.forename: Caren E
authors.initials: CE
authors.lastname: Smith
authors.forename: Kris
authors.initials: K
authors.lastname: Richardson
authors.forename: Duo
authors.initials: D
authors.lastname: Li
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Tucker
authors.forename: Chao-Qiang
authors.initials: CQ
authors.lastname: Lai
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism; D001900:Boston; D004040:Dietary Carbohydrates / Q000378:metabolism*; D004041:Dietary Fats / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism*; D005260:Female; D006630:Hispanic or Latino; D006720:Homozygote; D006801:Humans; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D046988:Proteasome Endopeptidase Complex / Q000235:genetics* / Q000378:metabolism; D012737:Sex Factors; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D005229:Fatty Acids, Monounsaturated; D007328:Insulin; D046988:Proteasome Endopeptidase Complex; C548045:proteasome activator PA700 subunit p58, human