Differential Effects of Aging, Drinking and Exercise on Serum Cholesterol Levels Dependent on the PPARA‐V227A Polymorphism

Abstract

Differential Effects of Aging, Drinking andExercise on Serum Cholesterol Levels Dependent on the PPARA-V227A Polymorphism: Hisao NAITO, e t a l . D e p a r t m e n t o f O c c u p a t i o n a l a n d Environmental Health, Nagoya University Graduate School of Medicine-Peroxisome proliferatoractivated receptor α (PPAR α) plays a pivotal role in lipid metabolism. Our previous study reported that PPARA-V227A was a major polymorphism in Japanese, which was associated with markedly lower serum total cholesterol (TC) levels, which were significantly affected by alcohol drinking compared to subjects with the wild-type (PPARA-WT) allele. However, serum lipids are also associated with aging and exercise frequency. The objective of the present study was to evaluate the relationship between PPARA-V227A and these factors. Genetic analysis of the polymorphism was performed in 1058 Japanese men and 281 women, and the relationship with aging, drinking and exercise on serum lipids was analyzed in 989 men and 245 women after exclusion criteria had been applied. In men, drinking increased high-density lipoprotein cholesterol (HDL-C) levels in both PPARA-WT and A227 carriers, but to a significantly higher degree in the latter. In women, TC and low-density lipoprotein cholesterol (LDL-C) levels in the A227 carriers drinking at least once a week were significantly higher than in PPARA-WT carriers. TC and LDL-C levels in males with PPARA-WT increased with aging regardless of drinking habit, while LDL-C levels in the A227 drinking carriers were significantly lower in 45-yr-old or older subjects than in 35-to 45-yr-olds. In addition, no effect of exercising was observed in the A227 carriers, while increase in the HDL-C of the PPARA-WT carriers was exercise frequency dependent. These results suggest that the influence of drinking, aging or exercise on TC, LDL-C and HDL-C levels in the A227 carriers may be different from those in the PPARA-WT subjects. (J Occup Health 2007; 49: 353-362)

Genetic Polymorphisms in the HTR2C and Peroxisome Proliferator-Activated Receptors Are Not Associated with Metabolic Syndrome in Patients with Schizophrenia Taking Clozapine

“…Our study did not include a sufficient number of female patients, and only two female participants had the C allele of V227A. Other reports have described the association of the PPAR α V227A polymorphism with serum lipid concentrations according to age, drinking habits, and exercise status in Japanese individuals,24,34 but we did not consider exercise and dinking status. One previous study reported that the PPAR γ 161C/T polymorphism had no association with the overall prevalence of MetS, but that a decrease in the HDL-cholesterol component was less prevalent in normal female subjects with the T allele 35.…”

“…Many polymorphisms of the PPAR α gene, especially the PPAR α-V227A polymorphism in East Asians, have recently been described. This polymorphism has been studied in relation to the serum lipid concentration in the Asian population 24,25…”

Joint effect of longevity-associated mitochondrial DNA 5178 C/A polymorphism and alcohol consumption on risk of hyper-LDL cholesterolemia in middle-aged Japanese men

“…In addition to APOE ε2/ε3/ε4 allele types, several polymorphisms, such as apolipoprotein A5 gene polymorphism [22], apolipoprotein C-III gene polymorphism [23], peroxisome proliferator-activated receptor α gene polymorphism [24], cholesteryl ester transfer protein Taq 1B polymorphism [25] and promoter polymorphism of hepatic lipase gene [26], influence the effects of alcohol consumption on serum LDL cholesterol concentrations. Therefore, gene-gene-environment or gene-gene-gene-environment interactions with serum LDL cholesterol levels should be investigated.…”

PPAR-α as a Key Nutritional and Environmental Sensor for Metabolic Adaptation

“…Among women (n = 194), the mean serum TC and TG levels in carriers of the 227A allele were lower than in noncarriers (P = 0.046 and P = 0.038, respectively), and a stronger association between this SNP and TC concentration was observed in women younger than 45 y of age than in the total group of women (P = 0.023) (86). In addition, significant interactions between the V227A polymorphism and alcohol drinking habits were found for TC and TG when excluding subjects with possible familial hypertriglyceridemia ($518 mg/dL), suggesting that the PPAR-a activity in the 227A carrier group with no alcohol drinking may be higher than in the wildtype group, but it may become reduced in subjects who consume alcohol (70,90).…”