Toll-like receptor 6 Ser249Pro polymorphism is associated with lower left ventricular wall thickness and inflammatory response in hypertensive women.
BACKGROUND
Experimental data demonstrated that inactivation of toll-like receptor (TLR) pathway components attenuated left ventricular (LV) remodeling induced by pressure overload. This study investigated the impact of TLR6 Ser249Pro polymorphism on LV structure in hypertensive subjects.


METHODS
A sample of 443 patients (266 women and 177 men) was evaluated by clinical history, physical examination, analysis of inflammatory and metabolic parameters, echocardiography, and genotyping of the TLR6 variant. Moreover, the relationship between genotypes and in vitro responsiveness of peripheral blood monocytic cells to TLR agonists was also assessed.


RESULTS
Homozygous women for the TLR6 249Ser allele had lower LV posterior wall thickness (9.4 + or - 0.4 vs. 10.5 + or - 0.1 mm; P = 0.02), interventricular septum thickness (9.7 + or - 0.3 vs. 10.7 + or - 0.1 mm; P = 0.03), and LV relative wall thickness (0.39 + or - 0.02 vs. 0.44 + or - 0.01; P = 0.02) than women with other genotypes. These results were confirmed by stepwise regression analyses adjusted by potential confounders. Conversely, homozygous men for the 249Ser variant showed no differences in LV structure in comparison to males carrying the 249Pro allele. In addition, monocytes from hypertensive women homozygous for the 249Ser allele showed a lower release of tumor necrosis factor-alpha and interleukin-6 in response to zymosan (TLR6 agonist), but not to lipopolysaccharide (TLR4 agonist).


CONCLUSIONS
These data suggest that hypertensive women homozygous for the TLR6 249Ser polymorphism might exhibit lower LV wall thickness and reduced TLR6-mediated inflammatory response than females carrying the major allele.
Department of Internal Medicine, School of Medicine, University of Campinas, Campinas, Brazil.
Maria L
ML
Sales
Roberto
R
Schreiber
Maria C S
MC
Ferreira-Sae
Maruska N
MN
Fernandes
Cristiane S C
CS
Piveta
José A A
JA
Cipolli
Cátia C
CC
Cardoso
José R
JR
Matos-Souza
Bruno
B
Geloneze
Kleber G
KG
Franchini
Wilson
W
Nadruz
D000328:Adult; D005260:Female; D006352:Heart Ventricles / Q000000981:diagnostic imaging; D006801:Humans; D006973:Hypertension / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051216:Toll-Like Receptor 6 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000235:genetics* / Q000502:physiology
D015850:Interleukin-6; D051216:Toll-Like Receptor 6; D014409:Tumor Necrosis Factor-alpha