Center on Population Health and Aging

Genetic Risk Factors and Phenotypes in Population Research on Aging

Developed by David Vandenbergh and Keith Whitfield

GeneName	Symbol	Polymorphism	African-American Data	Phenotypes	Reference
Apolipoprotein E	APOE	Epsilon (E2, E3, E4)	No diff for any phenotype after adjusting	dementia, Alzheimer's disease (AD), and vascular dementia (VaD)	Fitzpatrick AL. J Am Geriatr Soc 2004, 52(2):195-204.
Apolipoprotein E	APOE	Epsilon (E2, E3, E4)	Cognitive impairment neg assoc with E2, but E4 reduced risk for Alz in Af-Caribbean	Alz, Vascular Dis	Stewart R, Dement Geriatr Cogn Disord 2001, 12(4):251-6.
Apolipoprotein E	APOE	Epsilon (E2, E3, E4)	E2 and Reduced LDL levels	LDL. HDL, tot Chol, Triglycerides	Pablos-Mendez A, Arterioscler Thromb Vasc Biol. 1997, 17(12):3534-41.
Peroxisome Proliferator-Activated Receptor Gamma	PPARgamma	Pro12Ala (replaces alinine for Proline at condon 12 at amino-terminus of the PPARgamm2 isoform)	No African American data: Findings: Amino Acid substitution associated with lower BMI-index (Deep et al 1998). Pro/Pro genotype associated with T2DM (Ren et al, 2002). 5 subsequent studies (Mancini et al, 1999; Ringel et al, 1999; Clement et al, 2000; Hara et al, 2000; Meirhaeghe et al, 2000) could not verify these findings. Altshuler et al (2000) evaluated 16 published articles comparing them to family controls. Found modest association between Pro allele and diabetes.	Insulin resistence; BMI	Literature Review: Gurnell M. 2003. Clinical Endocrinology 59: 267-277.
	PPARgamma	Pro12Ala	No African American data: Findings: Whole body insulin sensitivity was improved for carriers of the of the Ala allele. No association between genotype and Type II diabetes	Whole body insulin senstivity (measured in two different ways); type II diabetes	Ek J et al. Diabetologia 2001, 44: 1170-76
PPAR-gamma- Coactivator 1	PGC-1	Gly482Ser	No African American data: Findings: Pima Indians (sample); No association with either type 2 diabetes or BMI; *Gly/Gly genotypes had a ower mean insulin secretory response to intravenous and oral glucose, and a lower mean rate of lipid oxidation despite a larger mean abdominal adipocyte size a higher mean plasma free fatty acid concentration.	Diabetes related phenotypes	Muller YL et al. Diabetes 2003, 52: 895-898.
	PGC-1	tested: 7 polymorphisms and Gly482Ser was the only significant one.	No African American data: Findings: *Gly482Ser variant is more prevalent among typeII diabetic patients (1.34 genotype relative risk to Type II diabetes)	Type II diabetes	Ek J et al. Diabetologia 2001, 44: 2220-2226.
Angiotensinogen I- Converting Enzyme	ACE	A/G SNP	No A.A. Population is Africans and White Americans	hypertension, BP	HGVbase [SNP000006569]
	ACE	old A2350G new A11860G	No A.A., but in Nigerians, the G allele assoc. w/ increased SBP & DBP	SBP and ACE conc.	Zhu X et al, Am J Hum Genet. 2001, 68:1139-1148.
	ACE	old A-240T new A-262T	No A.A., but in Nigerians, the T allele is assoc w/ inc. SBP & DBP	SBP, DBP and ACE concentration	Zhu X et al, Am J Hum Genet. 2001, 68:1139-1148.
	ACE	A11599G and A15990G and A20060G and A239T	Haplotype blocks and family-based transmission/ disequilibrium tests AAAA transmitted more often in A.A. htn offspring.	hypertension	Zhu X et al, Hypertension 2003, 41(5): 1027-34.
	ACE	I/D	Significant correlation w/ ACE activity; weak relationship to BP	hypertension	Rotimi C et al, Hypertension. 1996; 27: 558-563.
Angiotensinogen	AGT	M235T	235T is high in A.A. as well as in Nigerians and Jamacains, relative to Whites. But hypertension is high only in A.A., relative to N & J, so a large environmental contribution.	hypertension	Rotimi C et al, Hypertension. 1996; 27: 558-563.
	AGT	C4072T	Assoc w/ hyp in European and Japanese but not A.A.	hypertension	Rotimi C et al, Hypertension. 1994; 24: 591-594.
	AGT	5 different SNPs	no assoc. w/ htn or AGT levels	htn and AGT level	Abstract: Wu X et al, J Hypertens. 2003; Oct;21 (10): 1815-8.
	AGT	M235T	In Afro-Caribbeans, there's a significant assoc. of M235T w/ BP and cholesterol metabolism in the "genetic context" of the RH blood group system.	BP , lipids, and lipoprotein conc.	Abstract: Robinson MT et al, J Hum Hypertens. 2004 May; 18 (5): 351-63
	AGT	A-217G	Frequency of A allele was 0.29 in hypertensives and 0.19 in normotensives.	hypertension	Jain S et al, Journal of Biologcal Chemistry 2002 Sept; 277 No.39 (27): 36889-36896
Angiotensinogen II receptor, subtype 1	AGTR1	A44221G	G allele increases risk of hypertension. This is the only single marker that could be associated w/ htn in A.A.	hypertension	Zhu X et al, Hypertension.2003 May;41(5): 1027-34
	AGTR1	A44221G and C43732T	This haplotype block is significantly associated w/ htn (CG is overtransmitted in htn offspring)	hypertension	Zhu X et al, Hypertension.2003 May;41(5): 1027-34
renin	REN	C-4021T and C-3212T	This block is assoc w/ htn in A.A. with haplotype CC being transmitted less often and TC and TT transmitted more often than expected.	hypertension	Zhu X et al, Hypertension.2003 May;41(5): 1027-34
interleukin-1B	IL-1B	C-511T	no A.A. data, and no significant difference in allelic frequency btwn CAD+ and CAD- individuals	coronary artery disease (CAD)	Vohnout B et al, Haematologica. 2003 Jan.;88 (01): 54-60
	IL-1B	RFLP (-511)	In diabetic A.A. this allele is acssociated with periodontal disease.	periodontal disease	Guzman S et al, J Periodontol. 2003 Aug;74 (8): 1183-90
	IL-1B	RFLP	In A.A. influences risk of early- onset periodontitis	early-onset pereodontitis	Abstract: Diehl SR et al, J Periodontol. 1999 Apr;70(4): 418-30
interleukin-1	IL-1		Candidate gene linking periodontal disease and cardiovascular disease	periodontal disease and cardiovascular disease	Review Abstract: Kornman KS and Duff GW, 2001. Dec; 6(1): 48-57
interleukin-1 receptor antagonist	IL1-RA	VNTR (86bp) in intron 2	no A.A. data, and no significant difference in allelic frequency btwn CAD+ and CAD- individuals	coronary artery disease (CAD)	Vohnout B et al, Haematologica. 2003 Jan.;88 (01): 54-60
		ACT			Kamboh MI,(1995). "APOE*4-associated Alzheimer's disease risk is modified by alpha 1-antichymotrypsin polymorphism." Nat Genet. Aug;10(4):486-8. Click here for full paper.

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