PMID- 26483964
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20151020
LR  - 20201001
IS  - 2075-8251 (Print)
IS  - 2075-8251 (Linking)
VI  - 7
IP  - 3
DP  - 2015 Jul-Sep
TI  - Genomic Study of Cardiovascular Continuum Comorbidity.
PG  - 89-99
AB  - Comorbidity or a combination of several diseases in the same individual is a 
      common and widely investigated phenomenon. However, the genetic background for 
      non-random disease combinations is not fully understood. Modern technologies and 
      approaches to genomic data analysis enable the investigation of the genetic 
      profile of patients burdened with several diseases (polypathia, disease 
      conglomerates) and its comparison with the profiles of patients with single 
      diseases. An association study featuring three groups of patients with various 
      combinations of cardiovascular disorders and a control group of relatively 
      healthy individuals was conducted. Patients were selected as follows: presence of 
      only one disease, ischemic heart disease (IHD); a combination of two diseases, 
      IHD and arterial hypertension (AH); and a combination of several diseases, 
      including IHD, AH, type 2 diabetes mellitus (T2DM), and hypercholesterolemia 
      (HC). Genotyping was performed using the "My Gene" genomic service 
      (www.i-gene.ru). An analysis of 1,400 polymorphic genetic variants and their 
      associations with the studied phenotypes are presented. A total of 14 polymorphic 
      variants were associated with the phenotype "IHD only," including those in the 
      APOB, CD226, NKX2-5, TLR2, DPP6, KLRB1, VDR, SCARB1, NEDD4L, and SREBF2 genes, 
      and intragenic variants rs12487066, rs7807268, rs10896449, and rs944289. A total 
      of 13 genetic markers were associated with the "IHD and AH" phenotype, including 
      variants in the BTNL2, EGFR, CNTNAP2, SCARB1, and HNF1A genes, and intragenic 
      polymorphisms rs801114, rs10499194, rs13207033, rs2398162, rs6501455, and 
      rs1160312. A total of 14 genetic variants were associated with a combination of 
      several diseases of cardiovascular continuum (CVC), including those in the 
      TAS2R38, SEZ6L, APOA2, KLF7, CETP, ITGA4, RAD54B, LDLR, and MTAP genes, along 
      with intragenic variants rs1333048, rs1333049, and rs6501455. One common genetic 
      marker was identified for the "IHD only" and "IHD and AH" phenotypes: rs4765623 
      in the SCARB1 gene; two common genetic markers, rs663048 in SEZ6L and intragenic 
      rs6501455, were identified for the "IHD and AH" phenotype and a combination of 
      several diseases (syntropy); there were no common genetic markers for the 
      "syntropy" and "IHD only" phenotypes. Classificatory analysis of the 
      relationships between the associated genes and metabolic pathways revealed that 
      lipid-metabolizing genes are involved in the development of all three CVC 
      variants, whereas immunity-response genes are specific to the "IHD only" 
      phenotype. The study demonstrated that comorbidity presents additional challenges 
      in association studies of disease predisposition, since the genetic profile of 
      combined forms of pathology can be markedly different from those for isolated 
      "single" forms of a disease.
FAU - Makeeva, O A
AU  - Makeeva OA
AD  - Research Institute of Medical Genetics, Nab. Ushayki, 10, Tomsk, 634050, Russia ; 
      Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Blvd., 
      6, Kemerovo, 650000, Russia.
FAU - Sleptsov, A A
AU  - Sleptsov AA
AD  - Research Institute of Medical Genetics, Nab. Ushayki, 10, Tomsk, 634050, Russia.
FAU - Kulish, E V
AU  - Kulish EV
AD  - Research Institute of Medical Genetics, Nab. Ushayki, 10, Tomsk, 634050, Russia.
FAU - Barbarash, O L
AU  - Barbarash OL
AD  - Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Blvd., 
      6, Kemerovo, 650000, Russia.
FAU - Mazur, A M
AU  - Mazur AM
AD  - Genoanalitika, Leninskie Gory, 1/77, Off. 102, Moscow, 119234, Russia.
FAU - Prokhorchuk, E B
AU  - Prokhorchuk EB
AD  - Genoanalitika, Leninskie Gory, 1/77, Off. 102, Moscow, 119234, Russia.
FAU - Chekanov, N N
AU  - Chekanov NN
AD  - Genoanalitika, Leninskie Gory, 1/77, Off. 102, Moscow, 119234, Russia.
FAU - Stepanov, V A
AU  - Stepanov VA
AD  - Research Institute of Medical Genetics, Nab. Ushayki, 10, Tomsk, 634050, Russia.
FAU - Puzyrev, V P
AU  - Puzyrev VP
AD  - Research Institute of Medical Genetics, Nab. Ushayki, 10, Tomsk, 634050, Russia ; 
      Siberian State Medical University, Moskovskiy Trakt, 2, Tomsk, 634050, Russia.
LA  - eng
PT  - Journal Article
PL  - Russia (Federation)
TA  - Acta Naturae
JT  - Acta naturae
JID - 101525823
PMC - PMC4610169
OTO - NOTNLM
OT  - association studies
OT  - cardiovascular continuum
OT  - comorbidity
OT  - genetic polymorphism
OT  - multifactorial diseases
OT  - syntropy
EDAT- 2015/10/21 06:00
MHDA- 2015/10/21 06:01
PMCR- 2015/07/01
CRDT- 2015/10/21 06:00
PHST- 2015/10/21 06:00 [entrez]
PHST- 2015/10/21 06:00 [pubmed]
PHST- 2015/10/21 06:01 [medline]
PHST- 2015/07/01 00:00 [pmc-release]
PST - ppublish
SO  - Acta Naturae. 2015 Jul-Sep;7(3):89-99.