Background: Although the genetic susceptibility to diabetes and ischemic heart disease (IHD) has been well demonstrated, studies aimed at exploring gene variations associated with diabetic IHD are still limited; Methods: Our study included 204 IHD cases who had been diagnosed with diabetes before the diagnosis of IHD and 882 healthy controls. Logistic regression was used to find the association of candidate SNPs and polygenic risk score (PRS) with diabetic IHD. The diagnostic accuracy was represented with AUC. Generalized multifactor dimensionality reduction (GMDR) was used to illustrate gene-gene interactions; Results: For IL6R rs4845625, the CT and TT genotypes were associated with a lower risk of diabetic IHD than the CC genotype (OR = 0.619, p = 0.033; OR = 0.542, p = 0.025, respectively). Haplotypes in the AGER gene (rs184003-rs1035798-rs2070600-rs1800624) and IL6R gene (rs7529229-rs4845625-rs4129267-rs7514452-rs4072391) were both significantly associated with diabetic IHD. PRS was associated with the disease (OR = 1.100, p = 0.005) after adjusting for covariates, and the AUC were 0.763 (p < 0.001). The GMDR analysis suggested that rs184003 and rs4845625 were the best interaction model after permutation testing (p = 0.001) with a cross-validation consistency of 10/10; Conclusions: SNPs and haplotypes in the AGER and IL6R genes and the interaction of rs184003 and rs4845625 were significantly associated with diabetic IHD.
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Univ Tokyo, Grad Sch Med, Dept Dev Med Sci, Tokyo, Japan
Univ Tokyo Hosp, Dept Pediat, Tokyo, Japan
Tokyo Metropolitan Neurol Hosp, Dept Neuropediat, Fuchu, JapanUniv Tokyo, Grad Sch Med, Dept Dev Med Sci, Tokyo, Japan
Hoshino, Ai
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Takahashi, Naoto
Oka, Akira
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Univ Tokyo Hosp, Dept Pediat, Tokyo, Japan
Saitama Childrens Med Ctr, Dept Neurol, Saitama, JapanUniv Tokyo, Grad Sch Med, Dept Dev Med Sci, Tokyo, Japan
Oka, Akira
Mizuguchi, Masashi
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Univ Tokyo, Grad Sch Med, Dept Dev Med Sci, Tokyo, Japan
Natl Rehabil Ctr Children Disabil, Dept Pediat, Tokyo, JapanUniv Tokyo, Grad Sch Med, Dept Dev Med Sci, Tokyo, Japan
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Narayana Hrudayalaya Hosp, Thrombosis Res Inst, Mary & Garry Weston Funct Genom Unit, Bangalore 560099, Karnataka, IndiaNarayana Hrudayalaya Hosp, Thrombosis Res Inst, Mary & Garry Weston Funct Genom Unit, Bangalore 560099, Karnataka, India
Maitra, Arindam
Shanker, Jayashree
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Narayana Hrudayalaya Hosp, Thrombosis Res Inst, Mary & Garry Weston Funct Genom Unit, Bangalore 560099, Karnataka, IndiaNarayana Hrudayalaya Hosp, Thrombosis Res Inst, Mary & Garry Weston Funct Genom Unit, Bangalore 560099, Karnataka, India
Shanker, Jayashree
Dash, Debabrata
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Narayana Hrudayalaya Hosp, Thrombosis Res Inst, Mary & Garry Weston Funct Genom Unit, Bangalore 560099, Karnataka, IndiaNarayana Hrudayalaya Hosp, Thrombosis Res Inst, Mary & Garry Weston Funct Genom Unit, Bangalore 560099, Karnataka, India
Dash, Debabrata
John, Shibu
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Thrombosis Res Inst, Elizabeth & Emmanuel Kaye Bioinformat & Stat Unit, Bangalore, Karnataka, IndiaNarayana Hrudayalaya Hosp, Thrombosis Res Inst, Mary & Garry Weston Funct Genom Unit, Bangalore 560099, Karnataka, India
John, Shibu
Sannappa, Prathima R.
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Narayana Hrudayalaya Hosp, Thrombosis Res Inst, Mary & Garry Weston Funct Genom Unit, Bangalore 560099, Karnataka, IndiaNarayana Hrudayalaya Hosp, Thrombosis Res Inst, Mary & Garry Weston Funct Genom Unit, Bangalore 560099, Karnataka, India
Sannappa, Prathima R.
Rao, Veena S.
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Thrombosis Res Inst, Tata Prote & Coagulat Unit, Bangalore, Karnataka, IndiaNarayana Hrudayalaya Hosp, Thrombosis Res Inst, Mary & Garry Weston Funct Genom Unit, Bangalore 560099, Karnataka, India
Rao, Veena S.
Ramanna, Jayakumar K.
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Thrombosis Res Inst, Clin Res Unit, Bangalore, Karnataka, IndiaNarayana Hrudayalaya Hosp, Thrombosis Res Inst, Mary & Garry Weston Funct Genom Unit, Bangalore 560099, Karnataka, India
Ramanna, Jayakumar K.
Kakkar, Vijay V.
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Univ London, London, EnglandNarayana Hrudayalaya Hosp, Thrombosis Res Inst, Mary & Garry Weston Funct Genom Unit, Bangalore 560099, Karnataka, India
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ANM, Lab Genet Hematol, CONICET, Inst Med Expt IMEX, Pacheco de Melo 3081, RA-1425 Buenos Aires, DF, ArgentinaANM, Lab Genet Hematol, CONICET, Inst Med Expt IMEX, Pacheco de Melo 3081, RA-1425 Buenos Aires, DF, Argentina
Bestach, Yesica
Palau Nagore, Virginia
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ANM, Lab Genet Hematol, CONICET, Inst Med Expt IMEX, Pacheco de Melo 3081, RA-1425 Buenos Aires, DF, ArgentinaANM, Lab Genet Hematol, CONICET, Inst Med Expt IMEX, Pacheco de Melo 3081, RA-1425 Buenos Aires, DF, Argentina
Palau Nagore, Virginia
Flores, Maria G.
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Hosp Gen Agudos CG Durand, Serv Hematol, Buenos Aires, DF, ArgentinaANM, Lab Genet Hematol, CONICET, Inst Med Expt IMEX, Pacheco de Melo 3081, RA-1425 Buenos Aires, DF, Argentina
Flores, Maria G.
Gonzalez, Jacqueline
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Hosp Gen Agudos CG Durand, Serv Hematol, Buenos Aires, DF, ArgentinaANM, Lab Genet Hematol, CONICET, Inst Med Expt IMEX, Pacheco de Melo 3081, RA-1425 Buenos Aires, DF, Argentina
Gonzalez, Jacqueline
Arbelbide, Jorge
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Hosp Italiano Buenos Aires, Serv Hematol, Buenos Aires, DF, ArgentinaANM, Lab Genet Hematol, CONICET, Inst Med Expt IMEX, Pacheco de Melo 3081, RA-1425 Buenos Aires, DF, Argentina
Arbelbide, Jorge
Watman, Nora
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Hosp Gen Agudos JM Ramos Mejia, Serv Hematol, Buenos Aires, DF, ArgentinaANM, Lab Genet Hematol, CONICET, Inst Med Expt IMEX, Pacheco de Melo 3081, RA-1425 Buenos Aires, DF, Argentina
Watman, Nora
Sieza, Yamila
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Hosp Interzonal Gen Agudos Gral San Martin, Serv Hematol, La Plata, Buenos Aires, ArgentinaANM, Lab Genet Hematol, CONICET, Inst Med Expt IMEX, Pacheco de Melo 3081, RA-1425 Buenos Aires, DF, Argentina
Sieza, Yamila
Larripa, Irene
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ANM, Lab Genet Hematol, CONICET, Inst Med Expt IMEX, Pacheco de Melo 3081, RA-1425 Buenos Aires, DF, ArgentinaANM, Lab Genet Hematol, CONICET, Inst Med Expt IMEX, Pacheco de Melo 3081, RA-1425 Buenos Aires, DF, Argentina
Larripa, Irene
Belli, Carolina
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ANM, Lab Genet Hematol, CONICET, Inst Med Expt IMEX, Pacheco de Melo 3081, RA-1425 Buenos Aires, DF, ArgentinaANM, Lab Genet Hematol, CONICET, Inst Med Expt IMEX, Pacheco de Melo 3081, RA-1425 Buenos Aires, DF, Argentina