Tumor necrosis factor alpha (TNFalpha) and its soluble receptor p75 (sTNF-R p75) in familial combined hyperlipidemia (FCHL).
OBJECTIVE
Familial combined hyperlipidemia (FCHL) is a genetic disorder of lipid metabolism associated with insulin resistance and abnormalities in fatty acid metabolism whose underlying mechanisms are largely unknown. Perturbations in the TNFalpha/TNF-R pathway may play a role in these abnormalities.


RESULTS
We determined plasma levels of TNFalpha and sTNF-R p75 in 85 FCHL patients (TC 245+/-45 mg/dl; TG 260+/-148 mg/dl; apoB 148+/-37 mg/dl) and in 29 age- and sex-matched normolipemic relatives (NL) (TC 187+/-22.8 mg/dl; TG 115+/-37 mg/dl; apoB 106+/-16 mg/dl). Thirty-four normolipemic subjects (TC 180+/-34 mg/dl; TG 107+/-42 mg/dl; apoB 95+/-22 mg/dl) were also included as unrelated controls (NC). Plasma free fatty acids (NEFA) were also measured and insulin sensitivity was evaluated by HOMA. Levels of sTNF-R p75 were significantly reduced in FCHL compared to NL (2.30+/-0.55 ng/ml vs. 2.64+/-0.88 ng/ml, p<0.05) but not compared to NC (2.35+/-0.68 ng/ml). HOMA values were comparable in all groups and did not show any relation with plasma levels of sTNF-R p75. Logistic analysis demonstrated that a low concentration of sTNF-R p75 was an independent predictor of the affected status within FCHL families, but this role was no longer evident when FCHL patients were compared to NC. In FCHL, age (p<0.001) was positively, and TG (p=0.029) and HDL-C (p=0.025) were negatively correlated with plasma concentrations of sTNF-R p75. In the other groups, age (in NL) and non-HDL-C (in NC) were significantly correlated with sTNF-R p75.


CONCLUSIONS
Although our data do not support a causative role of TNFalpha/TNF-R alterations in FCHL, they confirm that variation in TNF-R shedding may influence lipid phenotypic expression in FCHL families.
Cavallo
M G
MG
Dipartimento di Clinica e Terapia Medica Applicata, Università di Roma La Sapienza, Policlinico Umberto I, Viale del Policlinico, 155, 00161 Rome, Italy.
Montali
A
A
Monetini
L
L
Valente
L
L
Mariani
P
P
Bifolco
M
M
Sirinian
M I
MI
Antonini
T M
TM
Fioretti
F
F
Campagna
F
F
Verna
R
R
Arca
M
M
D000328:Adult; D000367:Age Factors; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D012995:Solubility; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D008076:Cholesterol, HDL; D018124:Receptors, Tumor Necrosis Factor; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha