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Evidence for substantial effect modification by gender in a large-scale genetic association study of the metabolic syndrome among coronary heart disease patients

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Abstract

Major genetic determinants of the metabolic syndrome — a clustering of abdominal obesity, high triglycerides, low HDL cholesterol, high blood pressure and high fasting glucose — remain elusive. We surveyed 207 single-nucleotide polymorphisms in 110 candidate genes among coronary artery disease patients, a population enriched for metabolic abnormalities. The number of abnormalities (0–5) was determined in the 214 male and 91 female patients, and the association with each polymorphism evaluated by means of ordinal regression analysis. Polymorphisms in eight genes, including LDLR, GBE1, IL1R1, TGFB1, IL6, COL5A2, SELE and LIPC, were associated with metabolic syndrome in the whole population (P values ranged from 0.047 to 0.008). Variants in seven additional genes showed significant gene by gender interaction. Among these, separate analyses in men and women revealed a strong association with a silent polymorphism in the low-density lipoprotein receptor-related protein gene, LRPAP1, among females (P=0.0003), but not males (P=0.292). Other genes associated only in females included THBS1, ACAT2, ITGB3, F2 and SELP (P values ranging from 0.032 to 0.002). Only one gene (PRCP) was significantly associated in men alone (P=0.039). Our results propose several new candidate genes for the metabolic syndrome and suggest that the genetic basis of this syndrome may be strongly modified by gender.

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Author information

Authors and Affiliations

  1. School of Public Health, San Diego State University, 5500 Campanile Drive, San Diego, CA, 92182-4162, USA

    Jeanette J. McCarthy

  2. Millennium Pharmaceuticals, Cambridge, Massachusetts, USA

    Joanne Meyer

  3. Cleveland Clinic Foundation, Cleveland, Ohio, USA

    David J. Moliterno & Eric J. Topol

  4. Duke University Medical Center, Durham, North Carolina, USA

    L. Kristin Newby

  5. University of Alabama Medical Center, Birmingham, Alabama, USA

    William J. Rogers

Authors
  1. Jeanette J. McCarthy
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  2. Joanne Meyer
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  3. David J. Moliterno
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  4. L. Kristin Newby
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  5. William J. Rogers
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  6. Eric J. Topol
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Corresponding author

Correspondence to Jeanette J. McCarthy.

Additional information

This work has been reported on behalf of the GeneQuest multicenter study, which involves the following investigators and coordinators: Eric J. Topol (chairperson) (Cleveland Clinic Foundation); David J. Moliterno, Ruth Cannata, Patricia Welsh, Monique Rosenthal (Cleveland Clinic Foundation, Cleveland, Ohio); Spencer B. King, III, William Anderson, Joe Jean Borowski, Kris Anderberg (Emory University Hospital, Atlanta, Georgia); David R. Holmes Jr, Charanjit Rihal, Sharon McIntire-Langworthy (Mayo Clinic, Rochester, Minnesota); William Rogers, Ann Snider (University of Alabama Medical Center, Birmingham, Alabama); L. Kristin Newby, Laura Drew (Duke University Medical Center, Durham, North Carolina); Dean Kereiakes, Eli Roth, Louise Wohlford (The Lindner Center for Clinical Cardiovascular Research, Cincinnati, Ohio); Anthony De Franco, Teresa Schrader (LeBauer Cardiovascular Research Foundation, Greensboro, North Carolina); Phillip Gainey, Sandra Arsenault (St. Joseph Hospital, Savannah, Georgia); Paul Casale, Joann Tuzi (Lancaster Heart Foundation, Lancaster, Pennsylvania); Jeffrey Anderson, Juli Jerman, Rob Pearson Ann Allen (Latter Day Saints Hospital, Salt Lake City, Utah); Sherwyn Schwartz, Sue Beasie (Diabetes and Glandular Associates, San Antonio, Texas); Frank Aguirre, Sandra Aubuchon, Kristin Weisbrod (St Louis University Hospital, St. Louis, Missouri); Jeffrey Carney, Muriel Harris (The Heart Group, Saginaw, Michigan); Jim Bengtson, Mary Adolphson (Michigan Heart and Vascular Institute, Ypsilanti, Michigan); John Rudoff, Sue Williams (Oregon Cardiology Clinic, PC, Portland, Oregon); Jeanette McCarthy, Laura Carleu (Millennium Pharmaceuticals, Cambridge, Massachusetts)

List of the polymorphisms evaluated

List of the polymorphisms evaluated

Gene symbol

Gene name

SNP

Mutation type

Variant frequency

Flanking sequence

A2M

alpha-2-macroglobulin

A2M_1

Mis (V/I)

0.32

CTCCAGAG[G/A]TCAAGTCC

ABCA1

ATP-binding cassette, subfamily A, member 1

ABCA1_1

Mis (R/K)

0.26

TTTGTGGCCTACCAA[G/A]GGAGAAACTGGCTGC

ACADM

acyl-Coenzyme A dehydrogenase, C4-C12 straight chain; MCAD

ACADM_1

Silent

0.26

TACAGAATATCCTGT[A/G]GAAAAACTAATGAGG

ACAT2

acetyl-Coenzyme A acetyltransferase 2

ACAT2_1

Mis (K/R)

0.41

TGGTGTCAACTAGAA[A/G]AGGTGAGTATATCAT

ACAT2

acetyl-Coenzyme A acetyltransferase 2

ACAT2_2

Silent

0.18

TGGTGCTGCAGCTGT[T/C]GTTCTTATGAAGAAG

ACE

angiotensin I converting enzyme (peptidyl-dipeptidase A) 1

DCP1_1

Silent

0.42

GAATGTGATGGCCAC[A/G]TCCCGGAAATATGAA

ACE

angiotensin I converting enzyme (peptidyl-dipeptidase A) 1

DCP1_2

Mis (P/L)

0.43

CGATGCTGGAGAAGC[C/T]GGCCGACGGGCGGGA

ACE

angiotensin I converting enzyme (peptidyl-dipeptidase A) 1

DCP1_3

Silent

0.38

GTACAAGGATCTGCC[C/T]GTCTCCCTGCGTCGG

ACE

angiotensin I converting enzyme (peptidyl-dipeptidase A) 1

DCP1_4

Silent

0.43

CTGCTCCAGGTACTT[T/C]GTCAGCTTCATCATC

ADRB2

adrenergic receptor, beta 2

ADRB2_1

Mis (E/Q)

0.44

CACGACGTCACGCAG[G/C]AAAGGGACGAGGTGT

AGT

angiotensinogen

AGT_1

Mis (M/T)

0.42

CTGGCTGCTCCCTGA[T/C]GGGAGCCAGTGTGGA

AGTR1

angiotensin receptor 1

AGTR1_1

3′UTR

0.30

ACTACCAAATGAGC[A/C]TTAGCTACTTTTCAGA

ANXA4

annexin IV; lipocortin IV

ANXA4_1

Mis (T/M)

0.16

TTGTGGGGATGATGA[C/T]GCCCACGGTGCTGTA

APOA1

apolipoprotein AI

APOA1_1

Promoter

0.17

AGCAGCAACAGGGCC[G/A]GGGCTGGGCTTATCA

APOB

apolipoprotein B

APOB_1

Mis (R/Q)

0.09

GGAAAAATGAAGTCC[G/A]GATTCATTCTGGGTC

APOB

apolipoprotein B

APOB_2

Silent

0.50

CAAATTCCGAGAGAC[C/T]CTAGAAGATACACGA

APOC3

apolipoprotein CIII

APOC3_1

3′UTR

0.08

GCCTATCCATCCTGC[C/G]AGCTCCTTGGGTCCT

APOE

apolipoprotein E

APOE_1

Mis (C/R)

0.13

GACATGGAGGACGTG[T/C]GCGGCCGCCT GGTGC

BDKRB1

bradykinin receptor B1

BDKRB1_1

Silent

0.16

GCACAGAGTGCTGCC[G/A]ACATTTATCATCTCC

BDKRB2

bradykinin receptor B2

BDKRB2_1

Silent

0.16

CAAGGAGATCCAGAC[G/A]GAGAGGAGGGCCACG

CCKBR

cholecystokinin B receptor

CCKBR_1

Mis (V/I)

0.05

TTCATCTTTGGCACC[G/A]TCATCTGCAAGGCGG

CCL2

chemokine (C-C motif) ligand 2

SCYA2_1

Silent

0.39

CCCAGTCACCTGCTG[T/C]TATAACTTCACCAAT

CD14

CD14 antigen

CD14_1

Promoter

0.49

TCCTTCCTGTTACGG[C/T]CCCCCTCCCTGAAAC

CD36

CD36 antigen; thrombospondin receptor

CD36_2

Promoter

0.42

GTGACTCATCAGTTC[A/C]TTCCTGTAAAATTC

CD36

CD36 antigen; thrombospondin receptor

CD36_3

Intronic

0.42

ATAATTTTTTTGCT[A/G]TCATAATCGCCTCAT

CD36

CD36 antigen; thrombospondin receptor

CD36_4

Silent

0.01

TTTGAGTTTGGTTCC[G/T]TACCCTGTTACTACC

CETP

choesterol ester transfer protein

CETP_1

Mis (A/P)

0.07

GTGACTACCGTCCAG[G/C]CCTCCTATTCTAAGA

CETP

choesterol ester transfer protein

CETP_2

Mis (I/V)

0.33

AGCAGCTCCGAGTCC[A/G]TCCAGAGCTTCCTGC

CETP

choesterol ester transfer protein

CETP_3

Silent

0.06

CTCTGAGCGAGTCTT[C/T]CACTCGCTGGCCAAG

CETP

choesterol ester transfer protein

CETP_4

Intronic

0.43

GAATCACTGGGGTTC[G/A]AGTTAGGGTTCAGAT

COL5A2

collagen, type V, alpha 2

COL5A2_1

Silent

0.18

CCCAACGGGCTCTCC[G/A]GGTACCTCTGGTCCT

COMP

cartilidge oligomeric matrix protein (TSP-5)

COMP_1

Mis (N/D)

0.05

CGCAACCAGGCCGAC[A/G]ACTGCCCTAGGGTAC

COMP

cartilidge oligomeric matrix protein (TSP-5)

COMP_2

3′UTR

0.16

GCACACAGGCCCTGC[C/T]GGCCTTCTCAGCCCT

CYBA

p22 phox

CYBA_1

Mis (H/Y)

0.36

CCCAGGGGACAGAAG[T/C]ACATGACCGCCGTGG

ECE1

endothelin converting enzyme 1

ECE1_1

Silent

0.28

TCTCATCAACACCAC[C/T]GACAGATGCCTGCTC

ECE1

endothelin converting enzyme 1

ECE1_2

Silent

0.06

GAGGGTCACTGCCGA[T/C]CAGCTCAGGAAAGCC

EDN1

endothelin 1

EDN1_1

Intronic

0.23

TTAAAGACTATTAAT[T/C]ACACTAATATAGTTT

EDN1

endothelin 1

EDN1_2

Mis (K/N)

0.20

CAAGCTGAAAGGCAA[G/T]CCCTCCAGAGAGCGT

EDN1

endothelin 1

EDN1_3

Silent

0.14

GGCAACAGACCGTGA[G/A]AATAGATGCCAATGT

EDNRA

endothelin A receptor

EDNRA_1

Intronic

0.39

ACAAGGCAACTGTGA[C/G]TCCGGGAATCTCTTC

EDNRB

endothelin B receptor

EDNRB_1

Silent

0.40

AAAAGATTGGTGGCT[G/A]TTCAGTTTCTATTTC

ESR1

estrogen receptor 1

ESR1_1

Silent

0.18

GGGTTTCCCTGCCAC[A/G]GTCTGAGAGCTCCCT

F10

coagulation factor X

F10_1

Silent

0.13

TTTCTGTGGTGGAAC[C/T]ATTTGAGCGAGT TC

F11

coagulation factor XI

F11_1

Silent

0.12

TGCGTCTGTTCGTGG[C/T]GAGTGGCCGTGGCAG

F11

coagulation factor XI

F11_2

Silent

0.03

AAGATGCACGGATGA[C/T]GTCCACTGCCACTTT

F11

coagulation factor XI

F11_3

Silent

0.13

TGGATTGCCCAGTAC[G/A]CGCATTAAAAAGAGC

F13A1

coagulation factor XIII A-1

F13A1_1

Mis (Q/E)

0.21

ATGACTGTGACAGTT[C/G]AGTTTACCAATCCTT

F13A1

coagulation factor XIII A-1

F13A1_2

Mis (L/P)

0.21

TCTACACCGGGGTCC[T/C]GAAGGCAGAATTCAA

F13A1

coagulation factor XIII A-1

F13A1_3

Intronic

0.20

GGGCAGGCAGTGCAG[A/G]GCTGTGGGAAGCTTT

F13A1

coagulation factor XIII A-1

F13A1_4

Mis (M/K)

0.24

ATGCCAATTTGCAAA[A/T]GGACATCTT CCTGGA

F2

coagulation factor II; prothrombin

F2_1

Mis (T/M)

0.12

CCGACAGCAGCACCA[C/T]GGGACCCTGGTGCTA

F2

coagulation factor II; prothrombin

F2_2

3′UTR

0.01

AAAGTGACTCTCAGC[G/A]AGCCTCAATGCTCCC

F2

coagulation factor II; prothrombin

F2_3

Intronic

0.06

CTGCCTCCTGTACCC[G/A]CCCTGGGAC AAGAAC

F5

coagulation factor V

F5_1

Mis (R/Q)

0.02

GATCCCTGGACAGGC[G/A]AGGAATACAGGTATT

F5

coagulation factor V

F5_2

Mis (N/T)

0.04

ACCTCATTGGCAAGA[A/C]CTCAGTTCT CAATTC

F5

coagulation factor V

F5_3

Intronic

0.26

AGAATGAGGCCCTGG[A/G]AGGACCCTC CTAGTG

F5

coagulation factor V

F5_4

Mis (V/M)

0.31

GACAGCAACATGCCT[G/A]TGGACATGAGAGAAT

F7

coagulation factor VII

F7_1

Silent

0.14

CTCCTGTCGGTGCCA[C/T]GAGGGGTACTCTCTG

F7

coagulation factor VII

F7_2

Mis (R/Q)

0.11

ATGCCACCCACTACC[A/G]GGGCACGTG GTACCT

F7

coagulation factor VII

F7_3

Intronic

0.11

GCTGCAGGTGCGTCC[G/A]GGGAGGTTTTCTCCA

F9

coagulation factor IX

F9_1

Mis (A/T)

0.30

CTCACCCGTGCTGAG[G/A]CTGTTTTTCCTGATG

FABP3

fatty acid binding protein 3

FABP3_1

Mis (K/R)

0.04

ACATTCTCACCCTAA[A/G]AACACACAGCACCTT

FASN

fatty acid synthase

FASN_1

Mis (V/I)

0.03

AGCAGCACCTCCCAC[G/A]TCCCGGAGGTGGACC

FGA

fibrinogen, alpha

FGA_1

Mis (T/A)

0.24

TCTGGACCTGGAAGT[A/G]CTGGAAGCTGGAACT

FGB

fibrinogen, beta

FGB_1

Silent

0.21

TGAGACTGTGAATAG[C/T]AATATCCCAACTAAC

FGB

fibrinogen, beta

FGB_2

Mis (R/K)

0.21

CATGGTACTCAATGA[G/A]GAAGATGAGTATGAA

FGB

fibrinogen, beta

FGB_3

Promoter

0.22

TGACAAGTAAATAAG[C/T]TTTGCTGGGAAGATG

FGB

fibrinogen, beta

FGB_4

Promoter

0.24

CTATTGATTTTAATG[A/G]CCCCTTTTGAAATAG

FGG

fibrinogen, gamma

FGG_1

Mis (G/R)

0.04

GGAGCTAAACAGAGC[G/A]GGCTTTACTTTATTA

GBE1

glucan (1,4-alpha)-branching enzyme 1 (gllycogen branching enzyme)

GBE1_1

Mis (T/A)

0.03

AACATGAGTGTCCTG[A/G]CTCCTTTTACTCCAG

GP1BA

glycoprotein 1B (platelet), alpha

GP1BA_1

Mis (T/M)

0.06

CCCCAGGGCTCCTGA[C/T]GCCCACACCCAAGCT

HFE

hemochromatosis

HFE_1

Mis (C/Y)

0.06

ATATACGT[G/A]CCAGGTGG

HRG

histidine-rich glycoprotein

HRG_1

Mis (H/R)

0.20

ATGGGGCCCAAAGAC[A/G]TTCTCATAATAATAA

HRG

histidine-rich glycoprotein

HRG_2

Mis (N/I)

0.39

CTCTAAAGCCAGACA[A/T]TCAGCCCTTTCCTCA

HSD17B4

hydroxysteroid (17 beta) dehydrogenase 4

HSD17B4_1

Mis (W/R)

0.10

CGCCTCAGTGGAGAC[T/C]GGAATCCCTTACACA

IL1A

interleukin 1, alpha

IL1A_1

Mis (A/S)

0.29

ATCAAGCCTAGGTCA[G/T]CACCTTTTAGCTTCC

IL1B

interleukin 1, beta

IL1B_1

Silent

0.21

AGAACCTATCTTCTT[C/T]GACACATGG GATAAC

IL1R1

interleukin 1 receptor, type 1

IL1R1_1

Mis (A/G)

0.03

ACTTATGTTATAATG[C/G]ACAAGCCATATTTAA

IL1R2

interleukin 1 receptor, type II

IL1R2_1

Intronic

0.02

CTCTGTCAGCCCCCG[C/A]ATCAACCTGACATGG

IL1RN

interleukin 1 receptor antagonist

IL1RN_1

Mis (S/G)

0.15

AGTGGCCCCACCACC[A/G]GTTTTGAGTCTGCCG

IL1RN

interleukin 1 receptor antagonist

IL1RN_2

Silent

0.28

CATCCGCTCAGACAG[T/C]GGCCCCACCACCAGT

IL1RN

interleukin 1 receptor antagonist

IL1RN_3

Intronic

0.28

CAACCAACTAGTTGC[T/C]GGATACTTGCAAGGA

IL6

interleukin 6

IL6_1

Promoter

0.41

CTAGTTGTGTCTTGC[C/G]ATGCTAAAGGACGTC

INS

insulin

INS_1

Intronic

0.29

CTCAGCCCTGCCTGTC[T/A]

IRS2

insulin receptor substrate 2

IRS2_1

Intronic

0.13

GTCACATGTCAGAGA[A/G]TATCATTAAAAGAAG

ITGA2B

integrin, alpha 2B

ITGA2B_1

Silent

0.36

CGTGTACCCCCAGGT[C/T]GGCTTCTTCAAGCGG

ITGA2B

integrin, alpha 2B

ITGA2B_2

Mis (I/S)

0.36

ACTGGGGGCTGCCCA[T/G]CCCCAGCCCCTCCCC

ITGB1

integrin, beta 1

ITGB1_1

Silent

0.09

TATGGACCTGTCTTA[T/C]TCAATGAAAGACGAT

ITGB1

integrin, beta 1

ITGB1_2

Silent

0.08

AGGAACATTATCTGC[A/C]AATTCTAGCAATGTA

ITGB2

integrin, beta 2; CD18

ITGB2_1

Silent

0.24

TTTCGCGGGCGACGG[A/G]AAGCTGGGCGCCATC

ITGB2

integrin, beta 2; CD18

ITGB2_2

Silent

0.24

ACTCTCCTCCAGGGT[C/A]TTCCTGGATCACAAC

ITGB3

integrin, beta 3

ITGB3_1

Mis (L/P)

0.16

TACAGGCCCTGCCTC[T/C]GGGCTCACCTCGCTG

ITGB3

integrin, beta 3

ITGB3_2

Silent

0.29

TTCCCAGCAGGACGA[G/A]TGCAGCCCCCGAGAG

ITGB3

integrin, beta 3

ITGB3_3

Silent

0.08

AGGCATTGTCCAGCC[T/C]AATGACGGGCAGTGT

ITGB3

integrin, beta 3

ITGB3_4

Silent

0.30

CGAGTGCAGCCCCCG[A/G]GAGGGTCAGCCCGTC

ITPKB

inositol 1,4,5-trisphosphate 3-kinase B

ITPKB_1

Silent

0.28

GGACCCCAACTCAGC[T/C]TTCCTGCATACCCTG

LDLR

low density lipoprotein receptor

LDLR_1

Silent

0.45

AAGCATCGATGTCAA[T/C]GGGGGCAACCGGAAG

LDLR

low density lipoprotein receptor

LDLR_2

Silent

0.46

CCCAGAGGATATGGT[T/C]CTCTTCCACAACCTC

LDLR

low density lipoprotein receptor

LDLR_3

Silent

0.11

AGTGGGCGACAGATG[C/T]GAAAGAAACGAGTTC

LDLR

low density lipoprotein receptor

LDLR_4

Silent

0.26

GCACACAACCACCCG[G/A]CCTGTTCCCGACACC

LIPA

lysosomal acid lipase A; acid cholesteryl ester hydrolase

LIPA_1

Mis (P/T)

0.32

TGTTTGGTTCTCTGG[C/A]CCCTGCATTCTGAGG

LIPA

lysosomal acid lipase A; acid cholesteryl ester hydrolase

LIPA_2

Mis (G/R)

0.11

AGGGGTCT[G/A]GAGGGAAA

LIPC

hepatic lipase

LIPC_1

Mis (V/M)

0.04

CCTCAGGTGGACGGC[G/A]TGCTAGAAAACTGGA

LIPC

hepatic lipase

LIPC_2

Silent

0.41

CTTCCAGGAATCTGT[T/G]CAACTCTCTCGAAGC

LIPC

hepatic lipase

LIPC_3

Mis (N/S)

0.37

CTCCAGATGATGCCA[A/G]TTTTGTGGATGCCAT

LIPC

hepatic lipase

LIPC_4

Silent

0.49

CATTCATACCTTTAC[C/G]CGGGAGCACATGGGC

LIPC

hepatic lipase

LIPC_5

Promoter

0.22

ACACAGTAGCTTTAA[G/A]TTGATTAATTTGGAA

LPL

lipoprotein lipase

LPL_1

Intronic

0.29

TATAGGATTTAAAGC[T/G]TTTATACTAA ATGTG

LRP1

low density lipoprotein-related protein 1 (alpha 2 macroglobulin receptor)

LRP1_2

Silent

0.27

TGAGTACCCGACCTG[C/T]GGCCCCAGTGAGTTC

LRP1

low density lipoprotein-related protein 1 (alpha 2 macroglobulin receptor)

LRP1_3

Silent

0.31

CTTCCGGCTGAAGGA[C/T]GACGGCCGGACGTGT

LRP1

low density lipoprotein-related protein 1 (alpha 2 macroglobulin receptor)

LRP1_4

Silent

0.31

CCCCTTCGGGCTGGC[C/T]GTGTATGGGGAGCAC

LRP1

low density lipoprotein-related protein 1 (alpha 2 macroglobulin receptor)

LRP1_5

Silent

0.31

TGAGGGCGAGCTCTG[C/T]GGTGAGGCCTGGTCC

LRP2

lipoprotein-related protein 2; glycoprotein 330 megalin low density

LRP2_1

Mis (A/T)

0.28

TCCAATGC[G/A]CATCTGGG

LRP2

lipoprotein-related protein 2; glycoprotein 330 megalin low density

LRP2_2

Mis (N/S)

0.31

GACAATGCATCCCCA[A/G]CTCCTGGGTGTGTGA

LRPAP1

low density lipoprotein-related protein-associated protein 1; RAP; MRAP

LRPAP1_1

Silent

0.10

CTACAGCACTGAGGC[T/C]GGTGAGTGCCCGCCC

LRPAP1

low density lipoprotein-related protein-associated protein 1; RAP; MRAP

LRPAP1_2

3′ Noncoding

0.27

CGAACTCTGAAGGCA[C/T]TGGGGAGCCCAGCCC

MMP9

matrix metalloproteinase 9; gelatinase B

MMP9_1

Mis (R/Q)

0.33

CAGGACTCTACACCC[G/A]GGACGGCAATGCTGA

MMP9

matrix metalloproteinase 9; gelatinase B

MMP9_2

Mis (Q/R)

0.14

ACGTCTTCCAGTACC[A/G]AGGTGAGGGCTGAGG

MMP9

matrix metalloproteinase 9; gelatinase B

MMP9_3

Mis (A/V)

0.02

GCTGCTGCTTTGCTG[C/T]CCCCAGACAGCGCCA

MOG

myelin oligodendrocyte glycoprotein

MOG_1

Mis (L/V)

0.23

AGATCACT[C/G]TTGGCCTC

MTHFR

methylenetetrahydrofolate reductase

MTHFR_1

Mis (A/V)

0.32

AGGTGTCTGCGGGAG[T/C]CGATTTCATCATCAC

NOS2A

nitric oxide synthase 2 (inducible, hepatocytes)

NOS2A_1

Silent

0.26

CCGGGACTTCTGTGA[C/T]GTCCAGCGCTACAAC

NOS2A

nitric oxide synthase 2 (inducible, hepatocytes)

NOS2A_2

Silent

0.20

GGCCCTGGTCCAAGG[C/T]ATCCTGGAGCGAGTG

NOS2A

nitric oxide synthase 2 (inducible, hepatocytes)

NOS2A_3

Mis (S/L)

0.20

AGAAACTGAAGAAAT[C/T]GCTCTTCATGCTGAA

NOS3

nitric oxide synthase 3 (endothelial); ENOS

NOS3_1

Mis (D/E)

0.31

GCAGGCCCCAGATGA[G/T]CCCCCAGAACTCTTC

P2RY1

purinergic receptor P2Y, G-protein coupled, 1 (ADP receptor)

P2RY1_1

Silent

0.03

CGCTGCCTTCCTGGC[C/T]GGTCCGGGTTCGTCC

P2RY1

purinergic receptor P2Y, G-protein coupled, 1 (ADP receptor)

P2RY1_2

Silent

0.15

ATCGATTTACCTGGT[A/G]ATCATTGTACTGACT

PAI2

serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 2

PAI2_1

Mis (S/C)

0.22

TTTTCGGCAGATTTT[C/G]CTCACCCTAAAACTA

PAI2

serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 2

PAI2_2

Mis (N/K)

0.22

GCATAAGATAACCAA[C/G]TGCATTTTATTTTTC

PAI2

serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 2

PAI2_3

Mis (N/D)

0.22

AATGCATCCACAGGG[A/G]ATTATTTACTGGAAA

PAI2

serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 2

PAI2_4

Intronic

0.21

TGTTTTTTTCTTCCT[C/G]TCTTTGCTTCTAGAT

PCSK1

proprotein convertase subtilisin/kexin type 1

PCSK1_1

Intronic

0.19

GAGCCAGGAGTGGTC[T/C]AGAGCCCGAGGGTGG

PDGFA

platelet derived growth factor, A chain

PDGFA_1

Silent

0.24

AGCTCACGGGGTCCA[C/T]GCCACTAAGCATGTG

PDGFRA

platelet derived growth factor receptor, alpha

PDGFRA_1

Silent

0.13

AGTGAGCTGGCAGTA[C/T]CCCATGTCTGAAGAA

PECAM1

platelet/endothelial cell adhesion molecule (CD31 antigen); ELAM1

PECAM1_1

Mis (N/S)

0.35

CCAAGCAGAAGGCTA[A/G]CAAGGAACAGGAGGG

PECAM1

platelet/endothelial cell adhesion molecule (CD31 antigen); ELAM1

PECAM1_2

Intronic

0.46

CCGAGAAGAACAGAT[G/A]ATCCCTGTATTTCAA

PECAM1

platelet/endothelial cell adhesion molecule (CD31 antigen); ELAM1

PECAM1_3

Silent

0.49

ACTGCAGAGTACCAG[C/G]TGTTGGTGGAAGGAG

PIK3R1

phosphatidylinositol 3-kinase, regulatory, 1

PIK3R1_1

Mis (M/I)

0.17

TATGAATAACAATAT[G/A]TCCTTACAAAATGCT

PLAU

plasminogen activator, urokinase

PLAU_1

Mis (P/L)

0.22

AGGTGGGCCTAAAGC[C/T]GCTTGTCCAAGAGTG

PLAU

plasminogen activator, urokinase

PLAU_2

Silent

0.10

GCTTGCTCACCACAA[C/T]GACATTGCCTTGCTG

PLCG1

phospholipase C, gamma 1

PLCG1_1

Mis (I/T)

0.46

ACGAGCTGACCTTCA[T/C]CAAGAGCGCCATCAT

PLCG1

phospholipase C, gamma 1

PLCG1_2

Mis (S/G)

0.17

CAGGAGTTCATGCTC[A/G]GCTTCCTCCGAGACC

PLOD2

lysine hydrolase 2

PLOD2_1

Intronic

0.51

TGAAATTTATTTTGG[G/A]TGAATGACTGGCATG

PON1

paraoxonase 1, serum, alt transcript 1

PON1_1

Mis (M/L)

0.29

CTGGCTCTGAAGAC[A/T]TGGAGATACTGCCTAA

PON2

paraoxonase 2, serum

PON2_1

Silent

0.22

TGAAGAAG[C/G]AGAAAATT

PPARG

peroxisome proliferative activated receptor, gamma

PPARG_1

Mis (P/A)

0.12

GATTCTCCTATTGAC[G/C]CAGAAAGCGATTCCT

PPARG

peroxisome proliferative activated receptor, gamma

PPARG_2

Silent

0.14

GATTGTCACGGAACA[C/T]GTGCAGCTACTGCAG

PRCP

prolylcarboxypeptidase (angiotensinase C)

PRCP_1

Mis (T/S)

0.03

AGGATATCACAGACA[C/G]TCTGGTTGCAGTCAC

PRCP

prolylcarboxypeptidase (angiotensinase C)

PRCP_2

Mis (E/D)

0.18

GGATGTGGCTGAGGA[A/C]CTGAAAGCTATGTTG

PROC

protein C

PROC_1

Silent

0.29

CTTCCTCAATTGCTC[T/G]CTGGACAACGGCGGC

PROC

protein C

PROC_2

Silent

0.36

GGCCCACTGCATGGA[T/C]GAGTCCAAGAAGCTC

PROS1

protein S (alpha)

PROS1_1

Silent

0.39

AGCTCACTCATGTCC[A/G]TCAGTTTGG AAAAAG

PTGS2

cyclooxygenase (COX2)

PTGS2_1

Silent

0.17

AATTATGAGTTATGT[C/G]TTGACATCCAGATCA

SAA1

serum amyloid A1, beta

SAA1_1

Mis (H/R)

0.12

AGAGATTCTTTGGCC[A/G]TGGTGCGGAGGACTC

SAA1

serum amyloid A1, beta

SAA1_2

Mis (K/R)

0.01

GGGGCAGGAGTGGCA[A/G]AGACCCCAATCACTT

SCARB1

scavenger receptor class B, member 1

SRB1_2

Silent

0.49

TCACTTCCTCAACGC[C/T]GACCCGGTT CTGGCA

SCARB1

scavenger receptor class B, member 1

SRB1_3

Silent

0.01

CCCCACCTATCGCTT[C/T]GTGGCTCCCAAAACC

SCARB1

scavenger receptor class B, member 1

SRB1_4

Mis (V/I)

0.01

GAGAGCGACTACATC[G/A]TCATGCCCAACATCC

SCARB1

scavenger receptor class B, member 1

SRB1_5

Intronic

0.05

AGC[C/G]TGCGGCCCCAGCTC

SCARB1

scavenger receptor class B, member 1

SRB1_6

Mis (G/S)

0.10

AGGCGCGCAGACATG[G/A]GCTGCTCCGCCAAAG

SCARB1

scavenger receptor class B, member 1

SRB1_7

Intronic

0.10

AGGGGAGGGTGGGCC[C/T]GGCCATGGCTGCTCG

SDC4

syndecan 4 (amphiglycan, ryudocan

SDC4_1

Mis (F/L)

0.38

TTCGCGCTGCTGCTG[T/C]TCTTCGTAGGCGGAG

SELE

E-selectin

SELE_1

Mis (S/R)

0.09

CCTAAACCTTTGGGT[G/T]AAAAGAACTCTTGAA

SELE

E-selectin

SELE_2

Mis (S/R)

0.08

ACCAATACATCCTGC[A/C]GTGGCCACGGTGAAT

SELL

L-selectin

SELL_1

Mis (P/S)

0.12

ATGGACTGTACTCAC[C/T]CTTTGGGAAACTTCA

SELL

L-selectin

SELL_2

Mis (F/L)

0.27

GGGCCCCAGTGTCAG[T/C]TTGGTAAGTCTCTTT

SELL

L-selectin

SELL_3

Silent

0.20

AACCAACAAATCTCT[C/T]ACTGAAGAA GCAGAG

SELP

P-selectin

SELP_1

Mis (T/P)

0.11

AATGGCCACTGGTCA[A/C]CTACCGTGCCAACCT

SELP

P-selectin

SELP_2

Mis (V/L)

0.10

CTTCCTACTCCAGGG[G/T]TGCAATGTCCAGCCC

SELP

P-selectin

SELP_3

Mis (S/N)

0.14

ACCTGGAAGCCCCCA[G/A]TGAAGGAACCATGGA

SELP

P-selectin

SELP_4

Mis (N/D)

0.06

TGTCATTTCTCTTGT[A/G]ACAATGGCTTTAAGC

SELPLG

P-selectin ligand

SELPLG_1

Mis (M/I)

0.06

CCAGAAAT[G/A]CTGAGGA

SERPINA5

protein C inhibitor; PCI, PLANH3; PAI3

SERPINA5_1

Mis (A/V)

0.10

TTGACCTCTACAGGG[C/T]CTTGGCTTCCGCTGC

SERPINA5

protein C inhibitor; PCI, PLANH3; PAI3

SERPINA5_2

Mis (K/E)

0.09

CAGAAAAGCTCAGAG[A/G]AGGAGCTGCACAGAG

SERPINC1

serine (or cysteine) proteinase inhibitor, clade C (antithrombin), member 1

AT3_1

Silent

0.36

GAGCCTGGCCAAGGT[G/A]GAGAAGGAACTCACC

SERPIND1

serine (or cysteine) proteinase inhibitor, clade D (heparin cofactor), member 1

HCF2_1

Silent

0.45

CCTCATCTACGAGCA[C/T]CGCACCAGCTGCCTG

SREBF2

sterol regulatory element binding protein 2

SREBF2_1

Mis (R/S)

0.04

CCCCCCACTCTCCAG[G/C]AGCTCCGTGCTCAAG

SREBF2

sterol regulatory element binding protein 2

SREBF2_2

Intronic

0.07

TGAGAGTGGTGGGGA[A/G]GAGCCTTGT CTTCTT

SREBF2

sterol regulatory element binding protein 2

SREBF2_3

Mis (A/G)

0.29

TTGCAGCTGCTGCCG[C/G]CAACCTACAAACCTG

TBXA2R

thromboxane A2 receptor

TBXA2R_1

Silent

0.36

GGACCCCTGGGTGTA[T/C]ATCCTGTTCCGCCGC

TGFBI

TGFBi

TGFBI_1

Silent

0.27

TTCTGTGCAGAGCCT[C/T]TGCATTGAGAACAGC

TGFBI

TGFBi

TGFBI_2

Silent

0.48

GAACTGTGCCCGGCT[C/G]CTGAAAGCCGACCAC

THBD

thrombomodulin

THBD_1

Intronic

0.37

TGAGATGTAAAAGGT[A/G]TTAAATTGATGTTGC

THBD

thrombomodulin

THBD_2

Mis (A/V)

0.19

CCGACTCGGCCCTTG[C/T]CCGCCACATTGGCAC

THBS1

thrombospondin I

THBS1_1

Mis (N/S)

0.10

CTGGCCCA[A/G]TGAGAACC

THBS1

thrombospondin I

THBS1_2

Silent

0.10

CAGCCCCCAGATGAA[T/C]GGGAAACCCTGTGAA

THBS1

thrombospondin I

THBS1_3

Intronic

0.15

ATGGGCTTGAGAAAA[C/T]CCCCAGGATCACTTC

THBS1

thrombospondin I

THBS1_5

Silent

0.15

CATCAGTGAGACCGA[T/C]TTCCGCCGATTCCAG

THBS1

thrombospondin I

THBS1_6

Silent

0.11

TCAGGAGTGTGACAA[A/G]AGATGTAAGCATCTT

THBS1

thrombospondin I

THBS1_7

Intronic

0.11

CCTCTGCACCCAGCC[C/T]GTTAGCATGAACCCT

THBS1

thrombospondin I

THBS1_8

Silent

0.03

TCGTCTCTGCAACAA[C/T]CCCNCACCCCAGTTT

THBS1

thrombospondin I

THBS1_9

Mis (A/T)

0.12

CTCTGCAACAACCCC[G/A]CACCCCAGTTTGGAG

THBS2

thrombospondin II

THBS2_1

3′UTR

0.13

TGCAAATGGGTGTGA[T/C]GCGGTTCCAGATGTG

THBS2

thrombospondin II

THBS2_2

3′UTR

0.29

AAATATCAATGGAAC[T/G]CAGAGATGAACATCT

THBS2

thrombospondin II

THBS2_3

Intronic

0.01

CTTCATTAAATGTAG[C/T]GACTGTCAACAGCGT

THBS2

thrombospondin II

THBS2_4

Intronic

0.13

ATGCCAAACAGGAAC[G/A]ATCCATAACTTTAGT

THBS4

thrombospondin IV

THBS4_1

Mis (A/P)

0.20

GAGTGTCGAAATGGA[G/C]CGTGCGTTCCCAACT

THBS4

thrombospondin IV

THBS4_3

Mis (G/S)

0.02

GCTTACCAGACCGTG[G/A]GCCTGGATCCTGAAG

THBS4

thrombospondin IV

THBS4_4

Intronic

0.50

AAGGCTGTCAGTCAG[C/T]GGGTGCTCGGATCTC

THPO

thrombopoietin

THPO_1

Intronic

0.51

CATCAGCATTGTCTC[A/G]TGTACAGCTCCCTTC

TIMP1

tissue inhibitor of metalloproteinase 1

TIMP1_1

Silent

0.48

CACTACCTGCAGTTT[T/C]GTGGCTCCCTGGAAC

VWF

von Willebrand factor

VWF_1

Silent

0.11

CCCCTTCAGCGAGGC[A/C]CAGTCCAAAGGGGAC

VWF

von Willebrand factor

VWF_2

Silent

0.12

GTACTTGGCCTCAAC[C/T]GCCACCAATGACTGT

VWF

von Willebrand factor

VWF_3

Mis (A/T)

0.38

GAAGGGCTCGAGTGT[A/G]CCAAAACGTGCCAGA

VWF

von Willebrand factor

VWF_4

Mis (V/L)

0.09

GACATCCTGCAGCGG[G/T]TGCGAGAGATCCGCT

VWF

von Willebrand factor

VWF_5

Silent

0.37

GCTGTCCCCCGTCTA[C/T]GCCGGGAAGACCTGC

ZNF239

zinc finger protein 239

ZNF239_1

Silent

0.21

CGCCTTTGCTCGTGC[C/G]GTGGACACACGGCTG

 

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McCarthy, J.J., Meyer, J., Moliterno, D.J. et al. Evidence for substantial effect modification by gender in a large-scale genetic association study of the metabolic syndrome among coronary heart disease patients. Hum Genet 114, 87–98 (2003). https://doi.org/10.1007/s00439-003-1026-1

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  • DOI: https://doi.org/10.1007/s00439-003-1026-1

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