title: Association of common JAK2 variants with body fat, insulin sensitivity and lipid profile.
abstract: The leptin signal is transduced via the JAK2-STAT3 (Janus kinase 2-signal transducer and activator of transcription-3) pathway at the leptin receptor. JAK2 also phosphorylates insulin receptor substrate, integral to insulin and leptin action and is required for optimum adenosine triphosphate-binding cassette transporter A1 (ABCA1)-dependent transport of lipids from cells to apolipoprotein A-1 (apoA-I). We hypothesized that common variation in the JAK2 gene may be associated with body fat, insulin sensitivity, and modulation of the serum lipid profile in the general population. Ten tagging single-nucleotide polymorphisms (SNPs) spanning the gene were genotyped in 2,760 white female twin subjects (mean age 47.3 +/- 12.6 years) from the St Thomas' UK Adult Twin Registry. Minor allele frequencies were between 0.170 and 0.464. The major allele of rs7849191 was associated with higher central fat (P = 0.030), percentage of central fat (P = 0.014) and waist circumference (P = 0.027) the major allele of rs3780378 with higher serum apoA (P = 0.026), total cholesterol (P = 0.014), low-density lipoprotein (LDL) cholesterol (P = 0.012) and lower triglyceride (P = 0.023). However, no associations were significant at a level which took account of multiple testing. Although JAK2 is a critical element in leptin and insulin signaling and has a role in cellular cholesterol transport, we failed to establish associations of common SNPs with relevant phenotypes in this human study.
authors.affiliation: Center for Population Genomics and Pharmacogenetics, Duke University, Durham, NC, USA.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Ge
authors.forename: Sakina B
authors.initials: SB
authors.lastname: Gooljar
authors.forename: Theodosios
authors.initials: T
authors.lastname: Kyriakou
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Collins
authors.forename: Ramasamyiyer
authors.initials: R
authors.lastname: Swaminathan
authors.forename: Harold
authors.initials: H
authors.lastname: Snieder
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.forename: Sandra D
authors.initials: SD
authors.lastname: O'Dell
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D053614:Janus Kinase 2 / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2