title: PARL Leu262Val is not associated with fasting insulin levels in UK populations.
abstract: OBJECTIVE
  PARL, the gene encoding presenilins-associated rhomboid-like protein, maps to chromosome 3q27 within a quantitative trait locus that influences components of the metabolic syndrome. Recently, an amino acid substitution (Leu262Val, rs3732581) in PARL was associated with fasting plasma insulin levels in a US white population (N=1031). This variant was also found to modify the positive association between age and fasting insulin. The aim of this study was to test whether these findings could be replicated in two UK population-based cohorts.
  
  
  METHODS
  Participants from the Medical Research Council Ely and Hertfordshire cohort studies were genotyped for this variant using a SNaPshot primer extension assay and Taqman assay respectively. Full phenotypic and genotypic data were available for 3,666 study participants.
  
  
  RESULTS
  Based on a dominant model, we found no association between the Leu262Val polymorphism and fasting insulin levels (p=0.79) or BMI (p=0.98). We did not observe the previously reported interaction between age and genotype on fasting insulin (p=0.14).
  
  
  CONCLUSIONS
  Despite having greater statistical power, our data do not support the previously reported association between PARL Leu262Val and fasting plasma insulin levels, a measure of insulin resistance. Our findings indicate that this variant is unlikely to be an important contributor to insulin resistance in UK populations.
authors.affiliation: Metabolic Disease Group, Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
authors.forename: K A
authors.initials: KA
authors.lastname: Fawcett
authors.forename: N J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: J
authors.initials: J
authors.lastname: Luan
authors.forename: H
authors.initials: H
authors.lastname: Syddall
authors.forename: C
authors.initials: C
authors.lastname: Cooper
authors.forename: S
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: I N M
authors.initials: IN
authors.lastname: Day
authors.forename: M S
authors.initials: MS
authors.lastname: Sandhu
authors.forename: I
authors.initials: I
authors.lastname: Barroso
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D015992:Body Mass Index; D015331:Cohort Studies; D005215:Fasting; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology; D007930:Leucine; D008297:Male; D045726:Metalloproteases / Q000235:genetics*; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D008957:Models, Genetic; D006113:United Kingdom; D014633:Valine
chemical_list: D007328:Insulin; D024101:Mitochondrial Proteins; D045726:Metalloproteases; C485223:PARL protein, human; D007930:Leucine; D014633:Valine