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Repeat Length Polymorphism of the Serotonin Transporter Gene Influences Pulmonary Artery Pressure in Heart Failure
Author(s) -
Olson Thomas Patrick,
Snyder Eric M,
Robert Robert P,
Turner Stephen T,
Johnson Bruce D
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a403
Subject(s) - ctl* , heart failure , medicine , pulmonary artery , serotonin transporter , genotype , cardiology , pulmonary hypertension , polymorphism (computer science) , ejection fraction , endocrinology , serotonin , biology , gene , immunology , genetics , immune system , receptor , cd8
Pulmonary hypertension is common in patients with heart failure (HF); however, for a given degree of left ventricular dysfunction, the range in pulmonary artery pressures (PAP) is large. Polymorphisms of a number of candidate genes have been implicated in contributing to smooth muscle dysfunction and remodeling of the pulmonary vasculature, including the serotonin transporter (5HTT) gene. Patients with HF may have mild tissue hypoxia, which may alter expression of 5HTT. This study examined the influence of a repeat length polymorphism in the promoter region of the 5HTT gene on differences in PAP in HF patients. Ninety HF patients (age=55±14yrs; LVEF=28±10%; NYHA=2.0±0.9) and 90 age and gender matched controls (CTL, age=51±15yrs; LVEF=63±7%) were recruited. Heart failure and CTL subjects were divided into 3 genotype groups, SS‐homozygotes for the short variant, LL‐homozygotes for the long variant and LS‐heterozygous condition. For both HF and CTL, SS n=20; LS n=41; LL n=29). PAP was calculated from the tricuspid regurgitant velocity. Age and gender did not differ between HF and CTL or among genotype groups. PAP was higher in HF compared to CTL (38.9±12.5 vs 27.7±8.2 mmHg, p<0.01, respectively) with a significant genotype effect in HF (SS=34.2±8.6 vs LS=38.2±11.4 vs LL=43.2±15.2 mmHg, p<0.05), but not in CTL. The HF group also demonstrated elevated left atrial diameter compared to CTL (HF 48.0±8.7 vs 32.8±4.8 mm, p<0.01, respectively) although no difference was seen within the HF group across genotypes. These results suggest that the LL variant of 5HTT is associated with elevated PAP in HF but not CTL. HL71478 and HL07111.