title: Gene-environment interactions in wet beriberi: effects of thiamine depletion in CD36-defect rats.
abstract: Selective vulnerability to thiamine deficiency is known to occur between individuals and within different tissues. However, no comprehensive explanation for this has been found, and there are no reports that reproduce the cardiovascular manifestations of human wet beriberi in animals. We hypothesized that the distinction of substrate reliance, namely, the primary dependency on glucose as substrate, could be an underlying factor in the selective vulnerability of thiamine deficiency. In the setting of impaired fatty acid entry, which occurs in CD36-defect rats, substrate reliance shifts from fatty acid to glucose, which would be expected to lead to a susceptibility to thiamine deficiency. Genomic DNA was analyzed for CD36 defects in three cognate strains of rats [spontaneously hypertensive rats (SHR)/NCrj, SHR/Izm, and Wistar-Kyoto (WKY)/NCrj], which identified the presence of a CD36 defect in SHR/NCrj rats but not in SHR/Izm and WKY/NCrj rats. Treatment with 2 wk of thiamine-depleted chow on 4-wk-old rats of each of these strains resulted in increased body and lung weight in the SHR/NCrj rats but not in the SHR/Izm and WKY/NCrj rats. The increased lung weight in the SHR/NCrj rats was accompanied with histological changes of congestive vasculopathy, which were not observed in either the SHR/Izm or the WKY/NCrj rats. Thiamine-deficient 12-wk-old SHR/NCrj rats demonstrated increased body weight (305.6 +/- 6.2 g in thiamine-deficient rats vs. 280.8 +/- 9.1 g in control; P < 0.0001), lactic acidemia (pH, 7.322 +/- 0.026 in thiamine-deficient rats vs. 7.443 +/- 0.016 in control; P < 0.0001; lactate, 2.42 +/- 0.28 mM in thiamine-deficient rats vs. 1.20 +/- 0.11 mM in control; P < 0.0001) and reduced systemic vascular resistance (4.61 +/- 0.42 x 104 dyn.s.cm-5 in thiamine-deficient rats vs. 6.55 +/- 1.36 x 104 dyn.s.cm-5 in control; P < 0.0001) with high cardiac output (186.0 +/- 24.7 ml in thiamine-deficient rats vs. 135.4 +/- 27.2 ml in control; P < 0.0019). In conclusion, SHR/NCrj rats harboring a genetic defect of long-chain fatty acid uptake present the relevant clinical cardiovascular signs of human wet beriberi, strongly indicating a close gene-environment interaction in wet beriberi.
authors.affiliation: Third Division, Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan. in3024@poh.osaka-med.ac.jp
authors.forename: Takao
authors.initials: T
authors.lastname: Tanaka
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Kono
authors.forename: Fumio
authors.initials: F
authors.lastname: Terasaki
authors.forename: Taigo
authors.initials: T
authors.lastname: Kintaka
authors.forename: Koichi
authors.initials: K
authors.lastname: Sohmiya
authors.forename: Takayuki
authors.initials: T
authors.lastname: Mishima
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kitaura
mesh_terms: D000821:Animal Feed; D000818:Animals; D001602:Beriberi / Q000209:etiology* / Q000235:genetics*; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004452:Echocardiography; D004777:Environment; D016678:Genome; D006439:Hemodynamics; D008168:Lung / Q000473:pathology; D016133:Polymerase Chain Reaction; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D013831:Thiamine / Q000008:administration & dosage; D013832:Thiamine Deficiency / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D018955:CD36 Antigens; D004247:DNA; D013831:Thiamine