Statistical analyses. Pairwise crude comparisons of lipid levels and lipid particle sizes among the study groups were carried out using the Mann-Whitney U-test because the distributions were skewed. Calculations were carried out using SAS version 6.12 (SAS Institute, Cary, North Carolina, United States) and Stata version 8.2SE (StataCorp, College Station, Texas, United States). Analyses of lipid parameters were stratified by sex, given that there are known differences between female and male lipid profiles and cardiovas- cular risks [49,50]. Results are expressed as mean (SE).

Author contributions. NB conceived and designed the experi- ments. GA, MR, and NB performed the experiments. GA, CBS, ARS, RBL, AB, and NB analyzed the data. GA, MR, CBS, ARS, RBL, AB, and NB contributed reagents/materials/analysis tools. GA, MR, CBS, ARS, RBL, AB, and NB wrote the paper.

In order to take into consideration the false positive associations resulting from multiple tests of the 66 SNP (Table S1), a Bonferroni correction was applied to determine the proper level of statistical significance, p ¼ 0.05/66 ¼ 0.0007.

Funding. This work has been supported by grants from the Paul Beeson Physician Faculty Scholar in Aging Award, the Ellison Medical Foundation Senior Scholar Award, NIH RO1 (AG-18728–01A1), the General Clinical Research Center (NIH M01-RR12248), and Diabetes Research and Training Center (NIH DK 20541) at the Albert Einstein College of Medicine, and the Baltimore VA Geriatric Research and Education Clinical Center.

For a comparison of the difference in APOC3 C((cid:1)641)A genotype frequencies between the groups, the chi-square test was performed. Genotype frequencies of all SNP were found to be in Hardy- Weinberg equilibrium. A (corrected) p-value less than 0.05 was considered the threshold for statistical significance. Given that this is a relatively homogeneous population, stratification was not applied, except to control for gender effects as noted above. The haplotype association test between cases (probands) and controls was performed

Competing interests. The authors have declared that no competing interests exist. &

Wang CS, M

onathy WJ, Kloer HU, Alaupovic P (

) Modulation of lipoprotein lipase activity by apolipoproteins. Effect of apolipoprotein C- III. J Clin Invest

:

–

Chhabra S, Narang R, Lakshmy R, Vasisht S, Agarwal DP, et al. (

) Apolipoprotein C

Ss

polymorphism in the risk assessment of CAD. Mol Cell Biochem

:

–

Minihane AM, Finnegan YE, Talmud P, Leigh-Firbank EC, Williams CM (

) Influence of the APOC

(cid:

)

T.G polymorphism on plasma lipid levels: Effect of age and gender. Biochim Biophys Acta

:

–

Russo GT, Meigs JB, Cupples LA, Demissie S, Otvos JD, et al. (

) Association of the Sst-I polymorphism at the APOC

gene locus with variations in lipid levels, lipoprotein subclass profiles and coronary heart disease risk:The Framingham offspring study. Atherosclerosis

:

–

Corella D, Guillen M, Saiz C, Portoles O, Sabater A, et al. (

) Associations of LPL and APOC

gene polymorphisms on plasma lipids in a Mediterranean population: Interaction with tobacco smoking and the APOE locus. J Lipid Res

:

–

Liu HK, Li XF, Zhang SZ, Ren Y, Yong X, et al. (

) Association of Sst I polymorphism in apolipoprotein C

gene with hypertriglyceridaemia in coronary atherosclerotic heart disease and type II diabetes mellitus in Chinese population. Yi Chuan Xue Bao

:

–

Onat A, Hergenc G, Sansoy V, Fobker M, Ceyhan K, et al. (

) Apolipoprotein C-III, a strong discriminant of coronary risk in men and a determinant of the metabolic syndrome in both genders. Atherosclerosis

:

–

Olivieri O, Bassi A, Stranieri C, Trabetti E, Martinelli N, et al. (

) Apolipoprotein C-III, metabolic syndrome, and risk of coronary artery disease. J Lipid Res

:

–

Gervaise N, Garrigue MA, Lasfargues G, Lecomte P (

) Triglycerides, apo C

and Lp B:C

and cardiovascular risk in type II diabetes. Diabetologia

:

–

Li GP, Wang JY, Yan SK, Chen BS, Xue H, et al. (

) Genetic effect of two

References

Cournil A, Kirkwood TB (

) If you would live long, choose your parents well. Trends in Genetics

:

–

Perls TT, Wilmoth J, Levenson R, Drinkwater M, Cohen M, et al. (

) Life- long sustained mortality advantage of siblings of centenarians. Proc Natl Acad Sci U S A

:

–

Perls TT, Bubrick E, Wager CG, Vijg J, Kruglyak L (

) Siblings of centenarians live longer. Lancet

:

Barzilai N, Shuldiner AR (

) Searching for human longevity genes: The future history of gerontology in the post-genomic era. J Gerontol A Biol Sci Med Sci

: M

–M

Atzmon G, Schechter C, Greiner W, Davidson D, Rennert G, et al. (

) Clinical phenotype of Families with longevity. J Am Geriatr Soc

:

–

Barzilai N, Atzmon G, Schechter C, Schaefer EJ, Cupples AL, et al. (

) Unique lipoprotein phenotype and genotype associated with exceptional longevity. JAMA

:

–

Geesaman BJ, Benson E, Brewster SJ, Kunkel LM, Blanche H, et al. (

) Haplotype-based identification of a microsomal transfer protein marker associatedwiththehumanlifespan.Pro

at

ca

c

SA

:

–

Groenendijk M, Cantor RM, de Bruin TW, Dallinga-Thie GM (

) The ap

I-CIII-AIV gene cluster. Atherosclerosis

:

–

Reaven GM (

) Banting lecture

Role of insulin resistance in human disease. Diabetes

:

–

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, et al. (

) Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia

:

–

Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, et al. (

) The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC

Report. JAMA

:

–

Wang JY, Yan SK, Chen BS, Xue H, et al. (2004) Genetic effect of two

Amdam GV, Simoes ZLP, Hagen A, Norberg K, Schroder K, et al. (