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Objectives To investigate the association between IL18RAP and body mass index (BMI) and obesity and to verify the effect of a polymorphism in the microRNA136 (MIR136) IL18RAP binding region. Design We analysed samples from two Spanish cross-sectional studies, VALCAR (Spanish Mediterranean coast) and Hortega (Spanish centre). These studies aimed at analysing cardiovascular risk and development of cardiovascular disease in the general population. Both populations correspond to regions with different characteristics. Setting Five IL18RAP single nucleotide polymorphisms were selected using the SYSNPs web tool and analysed by oligonucleotide ligation assay (SNPlex). For the MIR136 functional study, cells were transfected with plasmids containing different rs7559479 polymorphism alleles and analysed by luciferase reporter assays. Participants 1970 individuals (Caucasian, both genders): VALCAR (468) and Hortega (1502). Results rs2293225, rs2272127 and rs7559479 showed the following associations: rs7559479 G allele correlated with a higher obesity risk (P=0.01; OR=1.82; 95% CI 1.15 to 2.87 for the VALCAR group; P=0.033; OR=1.35; 95% CI 1.03 to 1.79 for the Hortega population) and higher body mass index (BMI) values (P=0.0045; P=0.1 for VALCAR and Hortega, respectively); a significant association with obesity (P=0.0024, OR=1.44, 95% CI 1.14 to 1.82) and increased BMI values (P=0.008) was found when considering both populations together. rs2293225 T allele was associated with lower obesity risk (P=0.036; OR=0.60; 95% CI 0.35 to 0.96) and lower BMI values (P=0.0038; OR=1.41) while the rs2272127 G allele was associated with lower obesity risk (P=0.028; OR=0.66; 95% CI 0.44 to 0.97) only in the VALCAR population. A reporter assay showed that the presence of the A allele in rs7559479 was associated with increased MIR136 binding to IL18RAP. Conclusions Our results suggest that polymorphisms in IL18RAP influence susceptibility to obesity. We demonstrated that the A allele in rs7559479 increases MIR136 binding, which regulates IL-18 system activity. [ABSTRACT FROM AUTHOR]

Background and Objective: The aim of our study is to analyze the effect and security of low-density lipoproteins (LDL) apheresis in familial hypercholesterolemia (FH) subjects who did not response to conventional intensive optimized medical treatment., Patients and Methods: Seven heterozygous FH subjects and one homozygous apoB familial defective were studied. All subjects were on secondary prevention with highest statins doses in association with other hypolipemiant drugs; the mean LDL-C reduction was 20%. All of them were treated with LDL apheresis (immunoabsorption) for a mean of 4.25 years., Results: LDL apheresis resulted in a 68.3% decrease in LDL-C and 58.2% in apoB plasma values (P<.001). After an average of 3 years of follow-up, the cardiovascular events disappeared in 4 out of 5 symptomatic patients while in one patient the events were reduced in 75%. Four moderate side effects were reported in 820 apheresis procedures., Conclusions: LDL apheresis is a well-tolerated and safe treatment in FH patients who do not response to intensive conventional optimized medical treatment. The main limitation is its economical cost and low accessibility., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Background and Objective: To compare 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) value as an indicator of oxidative stress situation between healthy and familial combined hyperlipidemic (FCH) subjects as a mixed dislipidemia with insulin resistance model and early coronary heart disease, and to study its relationship with clinical-biologic parameters of insulin resistance., Subjects and Method: 40 non-related FCH patients (15 women) and 20 normolipidemic and nondiabetic healthy subjects (8 women) were studied. Clinical, anthropometric and biochemical parameters (lipidic profile, glucemia, insulinemia and 8-oxo-dG) were measured in fasting state in all., Results: Both groups had similar age, body mass index blood pressure and waist perimeter values. Insulin and 8-oxo-dG values were significantly higher in FHC subjects. These differences were maintained after correcting by waist perimeter. 8-oxo-dG correlated positively with insulin and trygliceride; and negatively with high density lipoprotein cholesterol in FCH subjects., Conclusions: Insulin values are independently correlated with oxidative stress degree measured as 8-oxo-dG.