Postural changes in blood pressure associated with interactions between candidate genes for chronic respiratory diseases and exposure to particulate matter.
BACKGROUND
Fine particulate matter [aerodynamic diameter </= 2.5 mum (PM(2.5))] has been associated with autonomic dysregulation.


OBJECTIVE
We hypothesized that PM(2.5) influences postural changes in systolic blood pressure (DeltaSBP) and in diastolic blood pressure (DeltaDBP) and that this effect is modified by genes thought to be related to chronic lung disease.


METHODS
We measured blood pressure in participants every 3-5 years. DeltaSBP and DeltaDBP were calculated as sitting minus standing SBP and DBP. We averaged PM(2.5) over 48 hr before study visits and analyzed 202 single nucleotide polymorphisms (SNPs) in 25 genes. To address multiple comparisons, data were stratified into a split sample. In the discovery cohort, the effects of SNP x PM(2.5) interactions on DeltaSBP and DeltaDBP were analyzed using mixed models with subject-specific random intercepts. We defined positive outcomes as p < 0.1 for the interaction; we analyzed only these SNPs in the replicate cohort and confirmed them if p < 0.025 with the same sign. Confirmed associations were analyzed within the full cohort in models adjusted for anthropometric and lifestyle factors.


RESULTS
Nine hundred forty-five participants were included in our analysis. One interaction with rs9568232 in PHD finger protein 11 (PHF11) was associated with greater DeltaDBP. Interactions with rs1144393 in matrix metalloprotease 1 (MMP1) and rs16930692, rs7955200, and rs10771283 in inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) were associated with significantly greater DeltaSBP. Because SNPs associated with DeltaSBP in our analysis are in genes along the renin-angiotensin pathway, we then examined medications affecting that pathway and observed significant interactions for angiotensin receptor blockers but not angiotensin-converting enzyme inhibitors with PM(2.5).


CONCLUSIONS
PM(2.5) influences blood pressure and autonomic function. This effect is modified by genes and drugs that also act along this pathway.
Wilker
Elissa
E
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02215, USA. ewilker@hsph.harvard.edu
Mittleman
Murray A
MA
Litonjua
Augusto A
AA
Poon
Audrey
A
Baccarelli
Andrea
A
Suh
Helen
H
Wright
Robert O
RO
Sparrow
David
D
Vokonas
Pantel
P
Schwartz
Joel
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004781:Environmental Exposure; D005838:Genotype; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000502:physiology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000502:physiology; D008875:Middle Aged; D052638:Particulate Matter / Q000633:toxicity*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D055815:Young Adult
D004268:DNA-Binding Proteins; C506927:ITPR2 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; C493258:PHF11 protein, human; D052638:Particulate Matter; D014157:Transcription Factors; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1