title: Genetic variations at ABCG5/G8 genes modulate plasma lipids concentrations in patients with familial hypercholesterolemia.
abstract: OBJECTIVE
  To investigate the association of four common single nucleotide polymorphisms (SNPs) at ABCG5 (i7892A>G, i18429C>T, Gln604GluC>G, i11836G>A) and five at ABCG8 (5U145T>G, Tyr54CysA>G, Asp19HisG>C, i14222T>C, and Thr400LysG>T) with plasma lipids concentrations and to explore the interaction between those SNPs and smoking in patients with FH.
  
  
  RESULTS
  ABCG5/G8 SNPs were genotyped in 500 subjects with genetic diagnosis of FH. Carriers of the minor A allele at the ABCG5_i11836G>A SNP displayed significantly higher HDL-C concentrations (P=0.023) than G/G subjects. In addition, carriers of the minor G allele at the ABCG5_Gln604GluC>G SNP had significantly lower VLDL-C (P=0.011) and lower TG (P=0.017) concentrations than homozygous C/C. Interestingly, a significant gene-smoking interaction was found, in which carriers of the minor alleles at ABCG5 (i7892A>G, i18429C>T, i11836G>A) SNPs displayed significantly lower HDL-C, higher TC and higher TG respectively, only in smokers. On the other hand, nonsmokers carriers of the minor alleles at ABCG5 (i18429C>T and Gln604GluC>G) SNPs had significantly lower TG concentrations (P=0.012 and P=0.035) compared with homozygous for the major allele.
  
  
  CONCLUSIONS
  Our data support the notion that ABCG5/G8 genetic variants modulate plasma lipids concentrations in patients with FH and confirm that this effect could be influenced by smoking. Therefore, these results suggest that gene-environmental interactions can affect the clinical phenotype of FH.
authors.affiliation: Reina Sofia University Hospital, Lipids and Atherosclerosis Research Unit, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), University of Cordoba, Ciber Fisiopatologia Obesidad y Nutricion (CIBEROBN), Spain.
authors.forename: A
authors.initials: A
authors.lastname: Garcia-Rios
authors.forename: P
authors.initials: P
authors.lastname: Perez-Martinez
authors.forename: F
authors.initials: F
authors.lastname: Fuentes
authors.forename: P
authors.initials: P
authors.lastname: Mata
authors.forename: J
authors.initials: J
authors.lastname: Lopez-Miranda
authors.forename: R
authors.initials: R
authors.lastname: Alonso
authors.forename: F
authors.initials: F
authors.lastname: Rodriguez
authors.forename: A
authors.initials: A
authors.lastname: Garcia-Olid
authors.forename: J
authors.initials: J
authors.lastname: Ruano
authors.forename: J M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: F
authors.initials: F
authors.lastname: Perez-Jimenez
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D005192:Family Health; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics*; D008055:Lipids / Q000097:blood* / Q000737:chemistry; D008074:Lipoproteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D012907:Smoking
chemical_list: C416945:ABCG5 protein, human; C416946:ABCG8 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D008055:Lipids; D008074:Lipoproteins