摘要
BACKGROUND Type 1 diabetes(T1D)is a complex disease with a higher incidence in Europeans than other populations.The Colombians Living in Medellin(CLM)is admixed with ancestry contributions from Europeans,Native Americans(NAT)and Africans(AFR).AIM Our aim was to analyze the genetic admixture component at candidate T1D loci in Colombian individuals with the disease.METHODS Seventy-four ancestry informative markers(AIMs),which tagged 41 T1D candidate loci/genes,were tested by studying a cohort of 200 Northwest Colombia diseased individuals.T1D status was classified by testing for glutamic acid decarboxylase(GAD-65 kDa)and protein tyrosine-like antigen-2 autoantibodies in serum samples.Candidate loci/genes included HLA,INS,PTPN22,CTLA4,IL2RA,SUMO4,CLEC16A,IFIH1,EFR3B,IL7R,NRP1 and RNASEH1,amongst others.The 1,000 genome database was used to analyze data from 94 individuals corresponding to the reference CLM.As the data did not comply with a normal distribution,medians were compared between groups using the Mann-Whitney U-test.RESULTS Both T1D patients and individuals from CLM displayed mainly European ancestry(61.58 vs 62.06)followed by Native American(27.34 vs 27.46)and to a lesser extent the AFR ancestry(10.28 vs 10.65)components.However,compared to CLM,ancestry of T1D patients displayed a decrease of NAT ancestry at gene EFR3B(24.30 vs 37.10)and an increase at genes IFIH1(32.07 vs 14.99)and IL7R(52.18 vs 39.18).Also,for gene NRP1(36.67 vs 0.003),we observed a non-AFR contribution(attributed to NAT).Autoimmune patients(positive for any of two auto-antibodies)displayed lower NAT ancestry than idiopathic patients at the MHC region(20.36 vs 31.88).Also,late onset patients presented with greater AFR ancestry than early onset patients at gene IL7R(19.96 vs 6.17).An association analysis showed that,even after adjusting for admixture,an association exists for at least seven such AIMs,with the strongest findings on chromosomes 5 and 10(gene IL7R,P=5.56×10-6 and gene NRP1,P=8.70×10-19,respectively).CONCLUSION Although Colombian T1D patients have globally presented with higher European admixture,specific T1D loci have displayed varying levels of Native American and AFR ancestries in diseased individuals.
BACKGROUND Type 1 diabetes（T1 D） is a complex disease with a higher incidence in Europeans than other populations. The Colombians Living in Medellin（CLM） is admixed with ancestry contributions from Europeans, Native Americans（NAT） and Africans（AFR）.AIM Our aim was to analyze the genetic admixture component at candidate T1 D loci in Colombian individuals with the disease.METHODS Seventy-four ancestry informative markers（AIMs）, which tagged 41 T1 D candidate loci/genes, were tested by studying a cohort of 200 Northwest Colombia diseased individuals. T1 D status was classified by testing for glutamic acid decarboxylase（GAD-65 k Da） and protein tyrosine-like antigen-2 autoantibodies in serum samples. Candidate loci/genes included HLA, INS, PTPN22,CTLA4, IL2 RA, SUMO4, CLEC16 A, IFIH1, EFR3 B, IL7 R, NRP1 and RNASEH1,amongst others. The 1,000 genome database was used to analyze data from 94 individuals corresponding to the reference CLM. As the data did not comply with a normal distribution, medians were compared between groups using the Mann-Whitney U-test.RESULTS Both T1 D patients and individuals from CLM displayed mainly European ancestry（61.58 vs 62.06） followed by Native American（27.34 vs 27.46） and to a lesser extent the AFR ancestry（10.28 vs 10.65） components. However, compared to CLM, ancestry of T1 D patients displayed a decrease of NAT ancestry at gene EFR3 B（24.30 vs 37.10） and an increase at genes IFIH1（32.07 vs 14.99） and IL7 R（52.18 vs 39.18）. Also, for gene NRP1（36.67 vs 0.003）, we observed a non-AFR contribution（attributed to NAT）. Autoimmune patients（positive for any of two auto-antibodies） displayed lower NAT ancestry than idiopathic patients at the MHC region（20.36 vs 31.88）. Also, late onset patients presented with greater AFR ancestry than early onset patients at gene IL7 R（19.96 vs 6.17）. An association analysis showed that, even after adjusting for admixture, an association exists for at least seven such AIMs, with the strongest findings on chromosomes 5 and 10(gene IL7 R, P = 5.56 × 10-6 and gene NRP1, P = 8.70 × 10-19, respectively).CONCLUSION Although Colombian T1 D patients have globally presented with higher European admixture, specific T1 D loci have displayed varying levels of Native American and AFR ancestries in diseased individuals.
基金
Colciencias-Colombia grant No.111556933366
CODI-Universidad de Antioquia,and Scholarship from Colciencias,call No.727(from2015)
