One-Two PM Punch: Gene Combination Increases Vulnerability to Air Pollutant

[Guest guest]

Reply To: " Lourdes Salvador "

Subject: One-Two PM Punch: Gene Combination Increases Vulnerability to Air

Pollutant

Sent: November 3, 2007 5:34:38 PM

One–Two PM Punch: Gene Combination Increases Vulnerability to Air Pollutant

http://www.ehponline.org/docs/2007/115-11/ss.html#onet

Numerous epidemiologic studies have found a link between exposure to fine

particles (PM2.5) and increased morbidity and mortality. Other studies have

found evidence of some of the specific pathways through which this damage

occurs, but much remains unknown about the relative importance of these

pathways in humans. An international team of researchers has taken a step

toward filling that void through its discovery that the combination of two

genetic traits—a deletion of one gene and a polymorphism of another—combine

to significantly increase risk of oxidative stress and subsequent

cardiovascular disease in some people exposed to PM2.5 [EHP 115:1617–1622;

Chahine et al.]. http://www.ehponline.org/docs/2007/10318/abstract.html

One well-known indicator of potential cardiovascular problems is reduced

heart rate variability (HRV). When the heart is less able to vary its beat,

it can't respond as nimbly to challenges such as pollutants, microbes, or

emotional stresses. PM2.5 exposure has been linked with reduced HRV,

possibly in part by triggering oxidative stress.

Several genes are known to play a role in defending against oxidative

stress. Two of these include glutathione S-transferase-M1 (GSTM1) and heme

oxygenase-1 (HMOX-1). To determine whether these genes have a link with

reduced HRV, the team studied 476 older Boston-area males, almost all white,

for whom they had information on the two genes, as well as data for three

established indicators of HRV: standard deviation of normal-to-normal

intervals (SDNN), variation at high frequency (HF), and variation at low

frequency (LF). Ambient PM2.5 data came from a central stationary monitor,

which had sampled in the 48-hour period prior to HRV testing and had earlier

been shown to be a good proxy for personal exposures in the area. The team

accounted for confounders such as age, body mass index, smoking, and

prescription drug use.

Overall, they found that each 10-µg/m3 increase in PM2.5 was associated with

a statistically significant decrease in two measures of HRV (6.8% for SDNN

and 17.3% for HF). Decreases for all three indicators were greater in men

with either a GSTM1 deletion or a particular polymorphism of HMOX-1. But the

decreases were greatest in the men who had both the GSTM1 deletion and the

HMOX-1 polymorphism, dropping 12.7% for SDNN, 27.8% for HF, and 20.1% for

LF. This combination occurred in 48% of the subjects.

The researchers acknowledge that much more work needs to be done addressing

variables such as sex, age, race, geographic setting, pathway of damage, and

affected body system. But their findings lead them to conclude that at least

one combination of genetic traits increases vulnerability to oxidative

stress and cardiovascular damage from PM2.5.

Bob Weinhold

--------------------------------------------------------------------------------

Particulate Air Pollution, Oxidative Stress Genes, and Heart Rate

Variability in an Elderly Cohort

Chahine,1 Baccarelli,1,2 Augusto Litonjua,3 O.

,1,3 Helen Suh,1 Diane R. Gold,1,3 Sparrow,4 Pantel Vokonas,4

and Schwartz1

1Department of Environmental Health, Harvard School of Public Health,

Boston, Massachusetts, USA; 2Center of Molecular Epidemiology and Genetics;

and EPOCA Epidemiology Research Center, University of Milan and IRCCS

Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy;

3Channing Laboratory, Department of Medicine, Brigham and Women's Hospital,

Harvard Medical School, Boston, Massachusetts, USA; 4VA Normative Aging

Study, Veterans Affairs Boston Healthcare System and the Department of

Medicine, Boston University School of Medicine, Boston, Massachusetts, USA

Abstract

Background and objectives: We have previously shown that reduced defenses

against oxidative stress due to glutathione S-transferase M1 (GSTM1)

deletion modify the effects of PM2.5 (fine-particulate air pollution of <

2.5 µm in aerodynamic diameter) on heart rate variability (HRV) in a

cross-sectional analysis of the Normative Aging Study, an elderly cohort. We

have extended this to include a longitudinal analysis with more subjects and

examination of the GT short tandem repeat polymorphism in the heme

oxygenase-1 (HMOX-1) promoter.

Methods: HRV measurements were taken on 539 subjects. Linear mixed effects

models were fit for the logarithm of HRV metrics—including standard

deviation of normal-to-normal intervals (SDNN) , high frequency (HF) , and

low frequency (LF) —and PM2.5 concentrations in the 48 hr preceding HRV

measurement, controlling for confounders and a random subject effect.

Results: PM2.5 was significantly associated with SDNN (p = 0.04) and HF (p =

0.03) in all subjects. There was no association in subjects with GSTM1,

whereas there was a significant association with SDNN, HF, and LF in

subjects with the deletion. Similarly, there was no association with any HRV

measure in subjects with the short repeat variant of HMOX-1, and significant

associations in subjects with any long repeat. We found a significant

three-way interaction of PM2.5 with GSTM1 and HMOX-1 determining SDNN (p =

0.008) , HF (p = 0.01) and LF (p = 0.04) . In subjects with the GSTM1

deletion and the HMOX-1 long repeat, SDNN decreased by 13% [95% confidence

interval (CI) , –21% to –4%], HF decreased by 28% (95% CI, –43% to –9%) ,

and LF decreased by 20% (95% CI, –35% to –3%) per 10 µg/m3 increase in PM.

Conclusions: Oxidative stress is an important pathway for the autonomic

effects of particles.

Key words: air particles, air pollution, cardiovascular health, genetic

variation, GST, heart rate variability, HMOX-1, PM2.5. Environ Health

Perspect 115:1617–1622 (2007) . doi:10.1289/ehp.10318 available via

http://dx.doi.org/ [Online 20 August 2007]

--------------------------------------------------------------------------------\

------------------------

SOURCE: OCC-ENV-MED-L Digest for Saturday, November 03, 2007