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A Common Haplotype in NAPEPLD Is Associated With Severe Obesity in a Norwegian Population‐Based Cohort (the HUNT Study)
Author(s) -
Wangensteen Teresia,
Akselsen Hanne,
Holmen Jostein,
Undlien Dag,
Retterstøl Lars
Publication year - 2011
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.2010.219
Subject(s) - norwegian , medicine , haplotype , obesity , cohort , cohort study , population , demography , environmental health , genetics , genotype , gene , biology , philosophy , linguistics , sociology
Obesity has a strong genetic etiology involving numerous identified metabolic pathways and others not yet examined. We investigated the association between severe obesity and genetic variation in selected candidate genes, including three drug‐related genes: cannabinoid receptor 1 ( CNR1 ), N ‐acyl phosphatidylethanolamine phospholipase D ( NAPEPLD ), and gastric lipase ( LIPF ); and three genes related to inflammation: nicotinamide phosphoribosyltransferase, six‐transmembrane epithelial antigen of the prostate 4 ( STEAP4 ) and interleukin 18 ( IL‐18 ). Subjects were 1,632 individuals with severe obesity (BMI ≥35 kg/m 2 ) and 3,379 controls (BMI 20–24.9 kg/m 2 ) that took part in a Norwegian population based cohort study. Tagging single‐nucleotide polymorphisms (SNPs) of the coding region of these genes were analyzed. SNP‐haplotypes for each gene were constructed in order to analyze allelic, genotypic, and haplotypic association to obesity. A single SNPs rs17605251 in NAPEPLD was nominally associated with BMI ≥35 kg/m 2 ( P = 0.035). A common haplotype in NAPEPLD was associated with BMI ≥35 kg/m 2 , after correction for multiple testing. The allele frequency was 56.8% in cases and 60.3% in controls, giving an odds ratio (OR) of 0.87 (95% confidence interval (CI) 0.79, 0.95; P = 0.0016). Homozygosity for this haplotype was protective against obesity (OR 0.79 (CI 0.70–0.91); P = 0.00059). The SNP rs7913071 in LIPF was associated with obesity, but the association lost statistical significance after correction for multiple testing. The CNR1, IL‐18, STEAP4 , and nicotinamide phosphoribosyltransferase genes were not associated with obesity. In conclusion a common haplotype in NAPEPLD , an enzyme involved in endocannabinoid synthesis, was protective against obesity.