The functional Toll-like receptor 4 Asp299Gly polymorphism is associated with lower left ventricular mass in hypertensive women.
BACKGROUND
This study investigated the impact of a putative functional TLR4 polymorphism (Asp299Gly) on left ventricular (LV) structure in hypertensive subjects.


METHODS
A sample of 443 patients (266 women and 177 men) was evaluated by clinical history, physical examination, anthropometry, analysis of inflammatory and metabolic parameters, echocardiography and TLR4 Asp299Gly genotyping. In addition, the relationship between the polymorphism and in vitro lipopolysaccharide responsiveness of peripheral blood monocytic cells was also assessed.


RESULTS
Women carrying the 299Gly allele presented lower posterior wall thickness (p=0.01), interventricular septum thickness (p=0.04), LV mass (p=0.01) and LV mass index (p=0.03), as well as a reduced prevalence of LV hypertrophy (p=0.002), in comparison to women with the wild-type genotype. These results were confirmed by stepwise and logistic regression analyses adjusted for potential confounders. Conversely, the 299Gly allele did not influence LV structure in men. Furthermore, in vitro assays revealed that monocytes of either men or women heterozygous for the 299Gly allele presented a lower lipopolysaccharide-induced production of interleukin-6, compared to non-carriers.


CONCLUSIONS
The functional TLR4 Asp299Gly polymorphism is associated with lower LV mass in hypertensive women. These findings suggest that interactions among gender, LV remodeling and TLR4 gene variants may occur in hypertensive subjects.
Department of Internal Medicine, School of Medicine, University of Campinas, SP, Brazil.
Maria L
ML
Sales
Roberto
R
Schreiber
Maria C S
MC
Ferreira-Sae
Maruska N
MN
Fernandes
Cristiane
C
Piveta
José A A
JA
Cipolli
Antônio
A
Calixto
José R
JR
Matos-Souza
Bruno
B
Geloneze
Kleber G
KG
Franchini
Wilson
W
Nadruz
D000419:Albuminuria / Q000235:genetics / Q000652:urine; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D003404:Creatinine / Q000652:urine; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics; D004452:Echocardiography; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006352:Heart Ventricles / Q000473:pathology*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology* / Q000652:urine; D017379:Hypertrophy, Left Ventricular / Q000453:epidemiology / Q000235:genetics; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012727:Sex Characteristics; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D015850:Interleukin-6; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D003404:Creatinine