title: Association of LIPA gene polymorphisms with obesity-related metabolic complications among severely obese patients.
abstract: The lipase A, lysosomal acid, cholesterol esterase enzyme (LIPA) is involved in the hydrolysis of triglycerides (TGs) and cholesteryl esters (CEs) delivered to lysosomes. LIPA deficiency in human causes two distinct phenotypes characterized by intracellular storage of CE and derangements in the control of cholesterol production, namely the Wolman disease (WD) and the CE storage disease (CESD). To test the potential association of LIPA gene polymorphisms with obesity-related metabolic complications, promoter, exons, and intronic flanking regions of the LIPA gene were first sequenced in 25 individuals. From the 14 common polymorphisms identified, 12 tagging single-nucleotide polymorphisms (tSNPs) were genotyped in a cohort of 1,751 obese individuals. After adjustments for the effect of age, sex, diabetes, and medication, the C allele of SNP rs1051338 was associated with lower blood pressure (BP; systolic (SBP) P = 0.004; diastolic (DBP) P = 0.006). Three of the tested SNPs were associated with modifications of the plasma lipid profile. The G/G genotype of rs2071509 was associated with higher high-density lipoprotein cholesterol (HDL-C) levels (P = 0.009) and minor allele of rs1131706 was also associated with higher HDL-C (P = 0.004) and an association between rs3802656 and total cholesterol (total-C)/HDL-C ratio was identified (P = 0.04). These results thus suggest that LIPA polymorphisms contribute to the interindividual variability observed in obesity-related metabolic complications.
authors.affiliation: Nutraceuticals and Functional Foods Institute, Laval University, Quebec City, Quebec, Canada.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Guénard
authors.forename: Alain
authors.initials: A
authors.lastname: Houde
authors.forename: Luigi
authors.initials: L
authors.lastname: Bouchard
authors.forename: André
authors.initials: A
authors.lastname: Tchernof
authors.forename: Yves
authors.initials: Y
authors.lastname: Deshaies
authors.forename: Simon
authors.initials: S
authors.lastname: Biron
authors.forename: Odette
authors.initials: O
authors.lastname: Lescelleur
authors.forename: Laurent
authors.initials: L
authors.lastname: Biertho
authors.forename: Simon
authors.initials: S
authors.lastname: Marceau
authors.forename: Louis
authors.initials: L
authors.lastname: Pérusse
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Vohl
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D009767:Obesity, Morbid / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011792:Quebec / Q000453:epidemiology; D017422:Sequence Analysis, DNA; D002787:Sterol Esterase / Q000097:blood / Q000235:genetics*; D014280:Triglycerides / Q000097:blood*; D015223:Wolman Disease / Q000453:epidemiology / Q000235:genetics*
chemical_list: D014280:Triglycerides; C503451:LIPA protein, human; D002787:Sterol Esterase