TY  - JOUR
AB  - Polymorphisms of the human Delta-5 (FADS1) and Delta-6 (FADS2) desaturase genes have been recently described to be associated with the level of several long-chain n-3 and n-6 polyunsaturated fatty acids (PUFAs) in serum phospholipids. We have genotyped 13 single nucleotide polymorphisms (SNPs) located on the FADS1-FADS2-FADS3 gene cluster (chromosome 11q12-13.1) in 658 Italian adults (78% males; mean age 59.7 +/- 11.1 years) participating in the Verona Heart Project. Polymorphisms and statistically inferred haplotypes showed a strong association with arachidonic acid (C20:4n-6) levels in serum phospholipids and in erythrocyte cell membranes (rs174545 adjusted P value for multiple tests, P < 0.0001 and P < 0.0001, respectively). Other significant associations were observed for linoleic (C18:2n-6), alpha-linolenic (C18:3n-3) and eicosadienoic (C20:2n-6) acids. Minor allele homozygotes and heterozygotes were associated to higher levels of linoleic, alpha-linolenic, eicosadienoic and lower levels of arachidonic acid. No significant association was observed for stearidonic (C18:4n-3), eicosapentaenoic (C20:5n-3) and docosahexaenoic (C22:6n-3) acids levels. The observed strong association of FADS gene polymorphisms with the levels of arachidonic acid, which is a precursor of molecules involved in inflammation and immunity processes, suggests that SNPs of the FADS1 and FADS2 gene region are worth studying in diseases related to inflammatory conditions or alterations in the concentration of PUFAs.
AU  - Malerba, G.*
AU  - Schaeffer, L.*
AU  - Xumerle, L.*
AU  - Klopp, N.*
AU  - Trabetti, E.*
AU  - Biscuola, M.*
AU  - Cavallari, U.*
AU  - Galavotti, R.*
AU  - Martinelli, N.*
AU  - Guarini, P.*
AU  - Girelli, D.*
AU  - Olivieri, O.*
AU  - Corrocher, R.*
AU  - Heinrich, J.
AU  - Pignatti, PF.*
AU  - Illig, T.
C1  - 4123
C2  - 25255
SP  - 289-299
TI  - SNPs of the FADS gene cluster are associated with polyunsaturated fatty acids in a cohort of patients with cardiovascular disease.
JO  - Lipids
VL  - 43
IS  - 4
PB  - Springer
PY  - 2008
SN  - 0024-4201
ER  - 

TY  - JOUR
AB  - Pathologic plasma lipoprotein cholesterol levels play a key role in the development and pathogenesis of human atherosclerotic cardiovascular diseases. Plasma cholesterol homeostasis is regulated by genetic predispositions and environmental factors. Animal models showing aberrant plasma cholesterol levels are used for the identification and analysis of novel causative genes. Here, we searched for inherited hypocholesterolemia phenotypes in randomly mutant mice which may contribute to the detection of disease protective alleles. In the Munich ENU mouse mutagenesis project, clinical chemistry blood analysis was carried out on more than 15,500 G1 offspring and 230 G3 pedigrees of chemically mutagenized inbred C3H mice to detect dominant and recessive mutations leading to a decreased plasma total cholesterol level. We identified 66 animals consistently showing hypocholesterolemia. Transmission of the altered phenotype to the subsequent generations led to the successful establishment of 14 independent hypocholesterolemic lines. Line-specific differences were detected by clinical chemistry analysis of plasma HDL cholesterol, LDL cholesterol and triglycerides. Thus, we successfully established a novel panel of ENU-derived mutant mouse lines for their use in the identification of alleles selectively influencing the plasma cholesterol homeostasis. Such findings may be subsequently used for humans and other species.
AU  - Aigner, B.*
AU  - Rathkolb, B.*
AU  - Mohr, M.*
AU  - Klempt, M.*
AU  - Hrabě de Angelis, M.
AU  - Wolf, E.*
C1  - 4011
C2  - 24543
SP  - 731-737
TI  - Generation of ENU-induced mouse mutants with hypocholesterolemia: Novel tools for dissecting plasma lipoprotein homeostasis.
JO  - Lipids
VL  - 42
IS  - 8
PB  - Springer
PY  - 2007
SN  - 0024-4201
ER  -