Polymorphism at the TRIB1 gene modulates plasma lipid levels: insight from the Spanish familial hypercholesterolemia cohort study.
OBJECTIVE
rs17321515 SNP has been associated with variation in LDL-C, high density lipoprotein cholesterol and triglycerides concentrations. This effect has never been studied in patients with severe hypercholesterolemia. Therefore, our aims were to assess the association of the rs17321515 (TRIB1) SNP with plasma lipids concentrations and anthropometric variables and to explore the interaction between this SNP and some classic risk factors in patients with familial hypercholesterolemia (FH).


RESULTS
rs17321515 SNP was genotyped in 531 subjects with genetic diagnosis of FH. Homozygous A/A had significantly higher waist circumference compared with G/G subjects (P = 0.006) and carriers of the minor allele G (P = 0.039). Interestingly, smokers homozygous for the A allele displayed higher plasma triglycerides concentrations (P = 0.029), higher VLDL-C levels (P = 0.023) and higher TC/HDL-C ratio (P = 0.035) than carriers of the minor allele G. In addition, homozygous A/A with the presence of arcus cornealis displayed lower plasma ApoA-I levels (P = 0.024) and higher TC/HDL-C ratio (P = 0.046) than carriers of the minor allele G.


CONCLUSIONS
Smoking status and presence of arcus cornealis modulate the effect of rs17321515 (TRIB1) polymorphism on plasma lipids levels in patients with FH. These results could explain the differences in the susceptibility to coronary heart disease in these patients.
Garcia-Rios
A
A
Reina Sofia University Hospital, Instituto Maimonides de Investigacion Biomedica de Cordoba-IMIBIC, 14004 Cordoba, University of Cordoba, CIBER Fisiopatologia de la Obesidad y Nutricion, Spain.
Perez-Martinez
P
P
Mata
P
P
Fuentes
F
F
Lopez-Miranda
J
J
Alonso
R
R
Caballero
J
J
Mata
N
N
Perez-Jimenez
F
F
Ordovas
J M
JM
D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood; D001112:Arcus Senilis / Q000209:etiology; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D003327:Coronary Disease / Q000209:etiology; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000150:complications / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000037:antagonists & inhibitors; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013030:Spain / Q000453:epidemiology; D014280:Triglycerides / Q000097:blood
C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; C493170:TRIB1 protein, human; D014280:Triglycerides; D017346:Protein Serine-Threonine Kinases