Academic journal article Environmental Health Perspectives

GSTM1, GSTT1, and GSTP1 Polymorphisms and Associations between Air Pollutants and Markers of Insulin Resistance in Elderly Koreans

Academic journal article Environmental Health Perspectives

GSTM1, GSTT1, and GSTP1 Polymorphisms and Associations between Air Pollutants and Markers of Insulin Resistance in Elderly Koreans

Article excerpt

BACKGROUND: Previous studies have suggested that diabetes mellitus (DM) is an outcome of exposure to air pollution, and metabolic detoxification genes affect air pollution-related outcomes.

OBJECTIVES: We evaluated associations between air pollutants and markers of insulin resistance (IR), an underlying mechanism of type 2 DM, and effect modification by GSTM1, GSTT1, and GSTP1 genotypes among elderly participants in the Korean Elderly Environmental Panel (KEEP) study.

METHODS: We recruited 560 people [greater than or equal to] 60 years of age and obtained blood samples from them up to three times between 2008 and 2010. For air pollution exposure, we used ambient air pollutant [i.e., particulate matter [less than or equal to] 10 [micro]m in diameter (P[M.sub.10]), sulfur dioxide (S[O.sub.2]), ozone ([O.sub.3]), and nitrogen dioxide (N[O.sub.2])] monitoring data. We measured levels of fasting glucose and insulin and derived the homeostatic model assessment (HOMA) index to assess IR. Mixed-effect models were used to estimate associations between air pollutants and IR indices on the same day or lagged up to 10 days prior, and effect modification by GSTM1, GSTT1, and GSTP1 genotypes.

RESULTS: Interquartile range increases in P[M.sub.10], [O.sub.3], and N[O.sub.2] were significantly associated with IR indices, depending on the lag period. Associations were stronger among participants with a history of DM and among those with GSTM1-null, GSTT1-null, and GSTP1 AG or GG genotypes.

CONCLUSIONS: Our results suggest that P[M.sub.10], [O.sub.3], and NO2 may increase IR in the elderly, and that GSTM1-null, GSTT1-null, and GSTP1 AG or GG genotypes may increase susceptibility to potential effects of ambient air pollutants on IR.

KEY WORDS: air pollution, elderly, genetic polymorphism, insulin resistance. Environ Health Perspect 120:1378-1384 (2012). http://dx.doi.org/10.1289/ehp.1104406 [Online 25 June 2012]

Insulin resistance (IR) has been regarded as an important health issue because it affects the development of type 2 diabetes mellitus (DM) (Grattagliano et al. 2008; Marx 2002). The number of patients with DM has grown rapidly and is expected to continue to increase worldwide (Hoang et al. 2007; Marx 2002; Zarich 2006).

Recently, exposure to nitrogen dioxide (N[O.sub.2]) and proximity to roads (which serves as a proxy for traffic-related pollutant exposure) have been associated with DM (Brook et al. 2008; Puett et al. 2011). This result raised the possibility that DM is affected directly by air pollution exposure in addition to being an effect modifier for air pollution-associated diseases (Bateson and Schwartz 2004; Dubowsky et al. 2006; Hathout et al. 2002; O'Neill et al. 2005; Peel et al. 2007; Zanobetti and Schwartz 2001). Correlations between air pollution and markers of IR have also been reported in a cross-sectional study of children (Kelishadi et al. 2009).

Recent research has suggested that oxidative stress is a major biologic pathophysiological mechanism underlying the adverse health effects of air pollutants (Romieu et al. 2010). Therefore, genes involved in oxidative stress are logical candidates for studying air pollution x gene interactions. The human glutathione S-transferase genes are well-known oxidative stress-related detoxification enzymes. Deletions of the glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genes lead to null phenotypes completely lacking enzyme function. A polymorphic site at codon 105 (A to G substitution, resulting in a change of isoleucine to valine) of GST P1 alters enzyme-binding kinetics for some electrophilic substrates (Zimniak et al. 1994). We hypothesized that GSTM1, GSTT1, and GSTP1 polymorphisms may contribute to susceptibility to air pollution-related outcomes.

We conducted a longitudinal panel study of elderly Koreans to estimate the effects of air pollutants on fasting blood levels of glucose and insulin and the homeostatic model assessment (HOMA) index of IR, and evaluated effect modification by GSTM1, GSTT1, and GSTP1 genotypes. …

Search by... Author
Show... All Results Primary Sources Peer-reviewed

Oops!

An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.