Variation at the DPP4 locus influences apolipoprotein B levels in South Asians and exhibits heterogeneity in Europeans related to BMI

被引:12
作者
Bailey, Swneke D. [1 ]
Xie, Changchun [2 ]
Pare, Guillaume [2 ,3 ,4 ]
Montpetit, Alexandre [1 ,5 ,6 ]
Mohan, Viswanathan [7 ]
Yusuf, Salim [2 ,4 ,8 ]
Gerstein, Hertzel [2 ,4 ,8 ]
Engert, James C. [1 ,9 ,10 ]
Anand, Sonia S. [2 ,4 ,8 ]
机构
[1] McGill Univ, Dept Human Genet, Montreal, PQ, Canada
[2] Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada
[3] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON L8S 4K1, Canada
[4] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON L8S 4K1, Canada
[5] McGill Univ, Montreal, PQ, Canada
[6] Genome Quebec Innovat Ctr, Montreal, PQ, Canada
[7] Madras Diabet Res Fdn, Madras, Tamil Nadu, India
[8] McMaster Univ, Dept Med, Hamilton, ON L8S 4K1, Canada
[9] McGill Univ, Dept Med, Montreal, PQ, Canada
[10] McGill Univ, Royal Victoria Hosp, Div Cardiol, Ctr Hlth, Montreal, PQ H3A 1A1, Canada
基金
加拿大健康研究院;
关键词
ApoB; BMI; DPP-4; Genetics; Incretin; Interaction; LDL-cholesterol; SNPs; GENOME-WIDE ASSOCIATION; GLUCAGON-LIKE PEPTIDE-1; RISK-FACTORS; DIPEPTIDYL PEPTIDASE-4; MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; LIPID PROFILE; ETHNIC-GROUPS; TYPE-2; VILDAGLIPTIN;
D O I
10.1007/s00125-013-3142-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims/hypothesis 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= 7.98x10(-5)) in EpiDREAM. The observed association was replicated in the INTERHEART South Asians (one-sided p= 9.65x10(-3); combined two-sided p= 4.68x10-(-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 EpiDREAMethnicities, we tested for and found an interaction between rs4664443 and BMI for ApoB among the Europeans, the largest subgroup in EpiDREAM (p= 4.14x 10(-3) for interaction), observing an association with ApoB in Europeans with a BMI < 25 kg/m(2) (p= 2.35x10(-3)), but not with a BMI >= 25 kg/m (2)(p= 0.21). The association between rs4664443 and ApoB among all EpiDREAMindividuals with BMI < 25 kg/m(2) was significant (n= 2,972; p= 1.44x10(-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= 9.52x10(-7)). Conclusion/interpretation Variation at the DPP4 locus is associated with ApoB in South Asians and displays heterogeneity related to BMI in other ethnicities.
引用
收藏
页码:738 / 745
页数:8
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