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Association of LIPA Gene Polymorphisms With Obesity‐Related Metabolic Complications Among Severely Obese Patients
Author(s) -
Guénard Frédéric,
Houde Alain,
Bouchard Luigi,
Tchernof André,
Deshaies Yves,
Biron Simon,
Lescelleur Odette,
Biertho Laurent,
Marceau Simon,
Pérusse Louis,
Vohl MarieClaude
Publication year - 2012
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2012.52
Subject(s) - single nucleotide polymorphism , genotype , medicine , endocrinology , obesity , snp , allele , biology , genetics , gene
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.