Vitamin C levels in blood are influenced by polymorphisms in glutathione S-transferases

Our plain-English summary of Vitamin C levels in blood are influenced by polymorphisms in glutathione S-transferases, by A. Horska, C. Mislanova, S. Bonassi, et al (European Journal of Nutrition, 2011).

The study

• Authors: A. Horska, C. Mislanova, S. Bonassi, M. Ceppi, K. Volkovova, M. Dusinska
• Journal: European Journal of Nutrition
• Published: 2011;50(6):437-46
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: Glutathione S-transferases (GSTs) are intimately involved in combating oxidative stress and in detoxifying xenobiotics. Our objective was to examine possible interactions between polymorphisms in GST genes and plasma vitamin C, tocopherols and carotenoids in 149 reference subjects and 239 subjects occupationally exposed to mineral fibres (asbestos, rock wool, glass fibre), agents that induce oxidative stress.

Methods: Deletion of GSTM1 and GSTT1, and substitution 105Ile/Val in GSTP1 genes were determined by PCR, antioxidants in plasma were measured by HPLC.

Results: Tocopherols and carotenoids were affected by age, sex, smoking, occupational exposure to fibres, but not by GST polymorphisms. Vitamin C level was influenced by sex, smoking and occupational exposure. Subjects with deletion of GST had lower vitamin C levels compared with subjects carrying the functional gene variant. Vitamin C levels varied according to GSTM1 polymorphism in the whole group (p < 0.05), in all reference subjects (p < 0.05), in the asbestos factory reference group (p < 0.05), and according to GSTT1 polymorphism in reference group of the rock wool plant (p < 0.05). Vitamin C levels were approximately 20% lower in subjects with both functionally deficient genes in the whole group (p < 0.01) and in all non-exposed subjects (p < 0.05).

Conclusions: The correspondence of lower vitamin C levels with non-functional GST isoenzymes may indicate a causal connection between two antioxidant defence pathways, also the underlying mechanism is not yet clear. It seems that supplementation by natural antioxidants is particularly important for subjects with unfavourable genetic makeup and in those exposed to oxidative stress.

In plain English

This biomonitoring study from Slovakia measured antioxidants in the blood of 388 volunteers. Of these, 239 were workers with at least 5 years of occupational exposure to asbestos (61), rock wool (98) or glass fibre (80). The other 149 were reference subjects: administrative staff from each plant, plus 49 local residents near the asbestos factory. The researchers tested whether common variants in three glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) were linked to blood levels of vitamin C, tocopherols and carotenoids. Asbestos-exposed workers had lower vitamin C, beta-carotene and lycopene than their reference group. The fat-soluble antioxidants showed no consistent link to the gene variants. People lacking the GSTM1 gene had lower vitamin C across the whole group (28.8 versus 31.0 micromoles per litre). In a multiple regression analysis of the whole study group, people lacking both GSTM1 and GSTT1 had vitamin C levels 6.42 micromoles per litre lower than those with both genes working (95% confidence interval 1.85 to 10.98 lower; p = 0.006). The authors concluded this might imply a causal connection between the two antioxidant defences, though the mechanism remains to be established.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Cross-sectional biomonitoring (molecular epidemiology) study comparing exposed workers with reference subjects
• Who was studied: 388 volunteers, men and women, from 3 industrial areas of western and middle Slovakia, sampled in September to October 2000 (asbestos and rock wool factories) and September 2001 (glass fibre factory). There were 239 exposed workers and 149 reference subjects. The reference subjects were administrative staff of each plant (21, 43 and 36) plus 49 local residents recruited for the asbestos factory. They were matched to the exposed workers by age, sex and smoking habit.
• Exposure: At least 5 years of occupational exposure to asbestos (fibre type not specified), rock wool or glass fibre. The genes studied were deletion of GSTM1 and GSTT1 and the 105Ile/Val substitution in GSTP1.
• Main results:
  • In asbestos-factory workers compared with their reference group, plasma vitamin C was significantly lower (p = 0.011).
  • In asbestos-factory workers compared with their reference group, plasma beta-carotene (p = 0.001) and lycopene (p = 0.021) were significantly lower.
  • In multiple regression against the pooled reference subjects, vitamin C was lower in asbestos-factory workers (-4.29 micromoles per litre, p = 0.007) and in fibreglass-factory workers (-4.11 micromoles per litre, p = 0.003).
  • In the whole study group, vitamin C was 28.8 micromoles per litre in subjects lacking GSTM1 versus 31.0 in subjects with the gene (p = 0.042).
  • In the asbestos factory reference group, vitamin C was 27.8 micromoles per litre in subjects lacking GSTM1 versus 33.1 in subjects with the gene (p = 0.037).
  • In the rock wool plant reference group, vitamin C was 27.1 micromoles per litre in subjects lacking GSTT1 versus 36.6 in subjects with the gene (p = 0.015).
  • In the multiple regression analysis of the whole group, subjects lacking both GSTM1 and GSTT1 had vitamin C 6.42 micromoles per litre lower than those with both genes functional (95% CI -10.98 to -1.85; p = 0.006).
  • Within the reference group, subjects lacking both GSTM1 and GSTT1 had vitamin C 7.67 micromoles per litre lower (95% CI -14.58 to -0.77; p = 0.03).
  • No association was observed between GSTP1 variants and vitamin C.
  • For the fat-soluble antioxidants, the multivariate model gave no noteworthy result. The only exception was higher retinol in GSTP1 105Ile/Val subjects, which the authors did not consider biologically reliable because it appeared in only one group.
• The authors' conclusion: The authors concluded that lower vitamin C in subjects lacking GSTT1 and GSTM1 might imply a causal connection between GST enzymes and vitamin C in antioxidant defence, and that the exact mechanism remains to be established. They suggested higher intake of natural antioxidants seems particularly important for people with unfavourable genetic makeup and those exposed to oxidative stress.
• Limitations the authors state:
  • The genotyping method could not tell heterozygous carriers from homozygous wild-type carriers for the GSTM1 and GSTT1 deletions.
  • The smaller size of the reference group limited statistical significance.
  • Group sizes differ slightly between analyses because of missing values.
  • An earlier study by the same group in rural Slovak men did not find the same association.
  • The mechanism behind the association is not established.

Topics

Medical terms in this study, explained in our Lexicon: Glutathione (GSH), Oxidative Stress, Occupational Exposure.

Related studies

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• Are glutathione S transferases involved in DNA damage signalling? Interactions with DNA damage and repair revealed from molecular epidemiology studies — M. Dusinska, M. Staruchova, et al. (2012)
• Polymorphism of glutathione S-transferase M1 and lung cancer risk among African-Americans and Caucasians in Los Angeles County, California — S.J. London, A.K. Daly, et al. (1995)
• Genetic polymorphism for glutathione-S-transferase mu in asbestos cement workers — K. Jakobsson, A. Rannug, et al. (1994)
• Glutathione S-transferases GSTM1 and GSTT1 polymorphisms and asbestosis — A. Franko, M. Dodic-Fikfak, et al. (2007)
• Glutathione S-transferase and N-acetyltransferase genotypes and asbestos-associated pulmonary disorders — A. Hirvonen, S.T. Saarikoski, et al. (1996)

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