title: Variation at the DPP4 locus influences apolipoprotein B levels in South Asians and exhibits heterogeneity in Europeans related to BMI.
abstract: OBJECTIVE
  Dyslipidaemia, a common feature of type 2 diabetes, is characterised by an increase in atherogenic particles, quantifiable through apolipoprotein B (ApoB) levels. Genetic studies of lipid levels have focused on Europeans; a study in South Asians could identify novel genes.
  
  
  METHODS
  We tested 31,739 single nucleotide polymorphisms (SNPs) from ∼ 2,000 genes in 2,573 South Asians from the epidemiological arm of the Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) study (EpiDREAM) for association with ApoB and we tested two novel associations for replication in 1,181 South Asians from the INTERHEART case-control study.
  
  
  RESULTS
  The SNP, rs4664443, within DPP4 was associated with ApoB (p = 7.98 × 10(-5)) in EpiDREAM. The observed association was replicated in the INTERHEART South Asians (one-sided p = 9.65 × 10(-3); combined two-sided p = 4.68 × 10(-6)). The rs4664443 SNP was not associated with ApoB among five other EpiDREAM ethnicities. However, because South Asians had a significantly lower mean BMI compared with other EpiDREAM ethnicities, we tested for and found an interaction between rs4664443 and BMI for ApoB among the Europeans, the largest subgroup in EpiDREAM (p = 4.14 × 10(-3) for interaction), observing an association with ApoB in Europeans with a BMI <25 kg/m(2) (p = 2.35 × 10(-3)), but not with a BMI ≥ 25 kg/m(2) (p = 0.21). The association between rs4664443 and ApoB among all EpiDREAM individuals with BMI <25 kg/m(2) was significant (n = 2,972; p = 1.44 × 10(-5)) compared with those with a BMI ≥ 25 kg/m(2) (n = 11,559; p = 0.81), and there was evidence of association among all genotyped individuals with a BMI <25 kg/m(2), including the INTERHEART South Asians (n = 3,601; p = 9.52 × 10(-7)).
  
  
  CONCLUSIONS
  Variation at the DPP4 locus is associated with ApoB in South Asians and displays heterogeneity related to BMI in other ethnicities.
authors.affiliation: Department of Human Genetics, McGill University, Montreal, QC, Canada.
authors.forename: Swneke D
authors.initials: SD
authors.lastname: Bailey
authors.forename: Changchun
authors.initials: C
authors.lastname: Xie
authors.forename: Guillaume
authors.initials: G
authors.lastname: Paré
authors.forename: Alexandre
authors.initials: A
authors.lastname: Montpetit
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Hertzel
authors.initials: H
authors.lastname: Gerstein
authors.forename: James C
authors.initials: JC
authors.lastname: Engert
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Anand
mesh_terms: D000328:Adult; D001055:Apolipoproteins B / Q000097:blood*; D044466:Asian People; D015992:Body Mass Index; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People
chemical_list: D001055:Apolipoproteins B; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4