The Relationships Between FAM5C SNP (rs10920501) Variability and Metabolic Syndrome and Inflammation in Women With Coronary Heart Disease

Abstract

Introduction:

The leading cause of death among women is coronary heart disease (CHD), a multifactorial disease with polygenic heritability estimated at 50%. Polymorphisms in the family with sequence similarity 5, member C′ (FAM5C) gene have been associated with myocardial infarction (MI). FAM5C also corresponds directly with the inflammatory biomarker monocyte chemoattractant protein 1 (MCP-1) and metabolic syndrome.

Method:

The purpose of this descriptive gene association pilot study was to investigate the variability of FAM5C (rs10920501) in 91 women with CHD. The authors also examined the associations between the variability of FAM5C (rs10920501) and metabolic syndrome, inflammatory markers, and early onset CHD.

Results:

No women in this study with the homozygous variant (TT) had an MI. Women with a history of MI and the heterozygous (AT) genotype had a later age of onset of CHD compared to those with the homozygous wild type (AA; F(3, 34) = 5.00, p < .01). These findings suggest a protective effect of the T allele in women with a history of MI. The genotype of FAM5C rs10920501 explained approximately 7% of the variability of age of onset of CHD in women who have had an MI, while holding body mass index (BMI) and smoking history constant. There was no significant relationship between FAM5C (rs10920501) and metabolic syndrome or any inflammatory biomarkers in this sample.

Conclusion:

FAM5C remains a gene of interest in a complex disease process.

Keywords

women atherosclerosis metabolic syndrome inflammation obesity

Get full access to this article

View all access options for this article.

References

American Diabetes Association. (2003). Standards of medical care for patients with diabetes mellitus. Diabetes Care, 26, S33–S50.

Anderson

J. L.

Horne

B. D.

Kolek

M. J.

Muhlestein

J. B.

Mower

C. P.

Park

J. J.

… Carlquist

J. F.

(2008). Genetic variation at the 9p21 locus predicts angiographic coronary artery disease prevalence but not extent and has clinical utility. American Heart Journal, 156, 1155–1162.e2.

Applied Biosystems. (2006). TaqMan SNP genotyping assays protocol. Retrieved from http://www3.appliedbiosystems.com/cms/groups/mcb_support/documents/generaldocuments/cms_042998.pdf

Athyros

V. G.

Kakafika

A. I.

Karagiannis

Mikhailidis

D. P.

(2008). Do we need to consider inflammatory markers when we treat atherosclerotic disease?. Atherosclerosis, 200, 1–12.

Beckie

T. M.

Beckstead

J. W.

Groer

M. W.

(2010). The influence of cardiac rehabilitation on inflammation and metabolic syndrome in women with coronary heart disease. Journal of Cardiovascular Nursing, 25, 52–60.

Beckie

T. M.

Mendonca

M. A.

Fletcher

G. F.

Schocken

D. D.

Evans

M. E.

Banks

S. M.

(2009). Examining the challenges of recruiting women into a cardiac rehabilitation clinical trial. Journal of Cardiopulmonary Rehabilitation and Prevention, 29, 13–21.

Brown

T. M.

Vaidya

Rogers

W. J.

Waters

D. D.

Howard

B. V.

Tardif

J. C.

Bittner

(2008). Does prevalence of the metabolic syndrome in women with coronary artery disease differ by the ATP III and IDF criteria?. Journal of Women’s Health (Larchmt), 17, 841–847.

Chen

S. N.

Ballantyne

C. M.

Gotto

A. M.,

Jr Marian

A. J.

(2009). The 9p21 susceptibility locus for coronary artery disease and the severity of coronary atherosclerosis. BMC Cardiovascular Disorders, 9, 3.

Connelly

J. J.

Shah

S. H.

Doss

J. F.

Gadson

Nelson

Crosslin

D. R.

… Gregory

S. G.

(2008). Genetic and functional association of FAM5C with myocardial infarction. BMC Medical Genetics, 9, 33.

10.

Dupuis

Larson

M. G.

Vasan

R. S.

Massaro

J. M.

Wilson

P. W.

Lipinska

… Benjamin

E. J.

(2005). Genome scan of systemic biomarkers of vascular inflammation in the Framingham Heart Study: Evidence for susceptibility loci on 1q. Atherosclerosis, 182, 307–314.

11.

Feinberg

M. S.

Schwartz

Behar

(2008). Impact of metabolic syndrome in patients with acute coronary syndrome. Advances in Cardiology, 45, 114–126.

12.

Grundy

S. M.

Cleeman

J. I.

Daniels

S. R.

Donato

K. A.

Eckel

R. H.

Franklin

B. A.

… Costa

(2006). Diagnosis and management of the metabolic syndrome: An American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Current Opinion in Cardiology, 21, 1–6.

13.

Hauser

E. R.

Crossman

D. C.

Granger

C. B.

Haines

J. L.

Jones

C. J.

Mooser

… Krause

W. E.

(2004). A genome-wide scan for early-onset coronary artery disease in 438 families: The GENECARD Study. American Journal of Human Genetics, 75, 436–447.

14.

Hivert

M. F.

Sullivan

L. M.

Fox

C. S.

Nathan

D. M.

D’Agostino

R. B.,

Sr Wilson

P. W.

Meigs

J. B.

(2008). Associations of adiponectin, resistin, and TNFα with insulin resistance. Journal of Clinical Endocrinology and Metabolism, 93, 3165–3172.

15.

Humphries

S. E.

Ridker

P. M.

Talmud

P. J.

(2004). Genetic testing for cardiovascular disease susceptibility: A useful clinical management tool or possible misinformation?. Arteriosclerosis, Thrombosis, and Vascular Biology, 24, 628–636.

16.

International HapMap Project. (2011). Retrieved August 22, 2011, from http://hapmap.ncbi.nlm.nih.gov/cgi-perl/gbrowse/hapmap27_B36/#search

17.

Kawano

Nakatani

Mori

Ueno

Fukaya

Abe

… Matsuoka

(2004). Identification and characterization of novel developmentally regulated neural-specific proteins, BRINP family. Brain Research. Molecular Brain Research, 125, 60–75.

18.

Langefeld

C. D.

Wagenknecht

L. E.

Rotter

J. I.

Williams

A. H.

Hokanson

J. E.

Saad

M. F.

… Mitchell

B. D.

(2004). Linkage of the metabolic syndrome to 1q23-q31 in Hispanic families: The Insulin Resistance Atherosclerosis study family study. Diabetes, 53, 1170–1174.

19.

McBride

H. M.

Neuspiel

Wasiak

(2006). Mitochondria: More than just a powerhouse. Current Biology, 16, R551–R560.

20.

Millpore Technical Publications. (2005a Retrieved from http://www.millipore.com/userguides.nsf/a73664f9f981af8c852569b9005b4eee/743685055b264cb0852572590062c194/$FILE/HSEP-63K.MPX.pdf). Human sepsis/apoptosis LINCOplex kit (Protocol—HSEP-63K).,

21.

Millpore Technical Publications. (2005b, December Retrieved from http://www.millipore.com/userguides.nsf/a73664f9f981af8c852569b9005b4eee/018e9e0e26525c1185257259004e227e/$FILE/HCVD2-67BK.pdf). Human cardiovascular disease (CVD) panel 2 (acute-phase proteins) LINCOplex kit (Protocol—HCVD2-67BK),

22.

Millpore Technical Publications. (2006 Retrieved from http://www.millipore.com/userguides.nsf/a73664f9f981af8c852569b9005b4eee/506688139fe4c9a98525742c007755db/$FILE/MPXHCYTO-60K.pdf). Human cytokine LINCOplex kit single plex rantes (Protocol—HCYTO-60K-1RNTS),

23.

Mosca

Banka

C. L.

Benjamin

E. J.

Berra

Bushnell

Dolor

R. J.

… Wegner

N. K.

(2007). Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Journal of the American College of Cardiology, 49, 1230–1250.

24.

National Health Interview Survey. (2008). National Center for Health Statistics: Current smoking. Retrieved August 22, 2011, from http://www.cdc.gov/nchs/data/nhis/earlyrelease/200906_08.pdf

25.

National Institutes of Health, National Heart, Lung, and Blood Institute. (2003). Detection, evaluation, and treatment of high blood cholesterol in adults (Adult treatment panel III; NIH publication No. 01-3670). Retrieved from http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3xsum.pdf

26.

Paynter

N. P.

Chasman

D. I.

Buring

J. E.

Shiffman

Cook

N. R.

Ridker

P. M.

(2009). Cardiovascular disease risk prediction with and without knowledge of genetic variation at chromosome 9p21.3. Annals of Internal Medicine, 150, 65–72.

27.

Roger

V. L.

A. S.

Lloyd-Jones

D. M.

Adams

R. J.

Berry

J. D. Brown, T. M.

… Wylie-Rosett

(2011). Heart disease and stroke statistics—2011 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation, 123, e18–e123.

28.

Schunkert

Erdmann

Samani

N. J.

(2010). Genetics of myocardial infarction: A progress report. European Heart Journal, 31, 918–925.

29.

Torkamani

Topol

E. J.

Schork

N. J.

(2008). Pathway analysis of seven common diseases assessed by genome-wide association. Genomics, 92, 265–272.

30.

Wang

Ria

Kelmenson

P. M.

Eriksson

Higgins

D. C.

Samnegard

… Paigen

(2005). Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility. Nature Genetics, 37, 365–372.