title: The Leu262Val polymorphism of presenilin associated rhomboid like protein (PARL) is associated with earlier onset of type 2 diabetes and increased urinary microalbumin creatinine ratio in an Irish case-control population.
abstract: OBJECTIVE
  Environmental and genetic factors contribute to the evolution of type 2 diabetes (T2DM). Presenilin associated rhomboid like protein (PARL) is a mitochondrial protein that has been implicated in T2DM in both the rodent Psammomys obesus and in humans. The SNP variant (Leu262Val) in PARL has been shown to be associated with hyperinsulinaemia in an age-dependent manner in a US non-diabetic, cohort. However, this finding has not been replicated in UK cohorts. We studied Leu262Val associations in an Irish Caucasian T2DM case-control population.
  
  
  METHODS
  An RFLP-PCR assay using BstN I was used to assess Leu262Val genotype in a total of 613 subjects, 421 with T2DM and 192 controls.
  
  
  RESULTS
  In the control group genotype frequencies were as follows 27.37% (GG), 51.58% (CG) and 21.05% (CC), while in the group with T2DM 30.64% (GG), 47.74% (CG) and 21.62% (CC). We observed no association between Leu262Val variant and T2DM nor was there an association with plasma insulin concentrations or BMI. There was no interaction between age and fasting plasma insulin concentration. However, in the group with T2DM the C allele was associated with higher urinary albumin to creatinine ratio while the GG genotype was associated with an earlier age of onset of T2DM.
  
  
  CONCLUSIONS
  The Leu262Val polymorphism of PARL is not associated with markers of insulin resistance. However, in subjects with T2DM, genetic variation at this locus may indicate earlier onset of T2DM and increased susceptibility to nephropathy and cardiovascular complications.
authors.affiliation: Metabolic Research Unit, St. James's Hospital, Trinity College Dublin, Ireland.
authors.forename: M
authors.initials: M
authors.lastname: Hatunic
authors.forename: M
authors.initials: M
authors.lastname: Stapleton
authors.forename: E
authors.initials: E
authors.lastname: Hand
authors.forename: C
authors.initials: C
authors.lastname: DeLong
authors.forename: V E F
authors.initials: VE
authors.lastname: Crowley
authors.forename: J J
authors.initials: JJ
authors.lastname: Nolan
mesh_terms: D017668:Age of Onset; D000419:Albuminuria / Q000235:genetics*; D019943:Amino Acid Substitution; D000818:Animals; D016022:Case-Control Studies; D003404:Creatinine / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000652:urine; D003925:Diabetic Angiopathies / Q000235:genetics; D003928:Diabetic Nephropathies / Q000235:genetics*; D004195:Disease Models, Animal; D014644:Genetic Variation; D005849:Gerbillinae; D006801:Humans; D006946:Hyperinsulinism / Q000235:genetics; D007494:Ireland; D007930:Leucine; D045726:Metalloproteases / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D014633:Valine
chemical_list: D024101:Mitochondrial Proteins; D003404:Creatinine; D045726:Metalloproteases; C485223:PARL protein, human; D007930:Leucine; D014633:Valine