:

–

Clarke R, Refsum H, Birks J, et al. Screening for vitamin B-

and folate deficiency in older persons. Am J Clin Nutr.

;

:

–

Tan GD, Neville M, Liverani E, et al. The in vivo effects of Pro

Ala PPARg polymorphism on adipose tissue NEFA metabolism—the first use of the Oxford Biobank. Diabetologia.

;

:

–

Bengra C, Mifflin TE, Khripin Y, et al. Genotyping of essential hypertension single-nucleotide polymorphisms by a homogeneous PCR method with universal energy transfer primers. Clin Chem.

;

:

–

Stephens M, Smith NJ, Donnelly P. A new statistical method for haplotype reconstruction from population data. Am J Hum Genet.

;

:

–

Bathum L, Christiansen L, Tan Q, Vaupel J, Jeune B, Christensen K. No evidence for an association between extreme longevity and microsomal transfer protein polymorphisms in a longitudinal study of

nonagenarians. Eur J Hum Genet.

;

:

–

Ledmyr H, Karpe F, Lundahl B, M

innon M, Skoglund Andersson C, Ehrenborg E. Variants in the microsomal triglyceride transfer protein gene are associated with plasma cholesterol and body mass index. J Lipid Res.

;

:

–

Phillips C, Mullan K, Owens D, Tomkin GH. Microsomal triglyceride transfer protein polymorphisms and lipoprotein levels in type

diabetes. QJM.

;

:

–

Lundahl B, Leren TP, Ose L, Hamsten A, Karpe F. A functional polymorphism in the promoter region of the microsomal triglyceride transfer protein (MTP -

G/T) influences lipoprotein phenotype in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol.

;

:

–

Couture P, Otvos JD, Cupples LA, Wilson PW, Schaefer E. Absence of association between genetic variation in the promoter of the microsomal triglyceride transfer protein gene and plasma lipoproteins in the Framingham Offspring Study. Atherosclerosis.

;

:

–

MTTP D98E, respectively), and only one of each pair was typed in the older population. The remaining five HapMapII SNPs represent 51% of the variation within this region at an r2 . 0.5, whereas 44% of the variation was seen at an r2 . 0.8. However, the five additional SNPs we used (not included in HapMap II) (MTTP-410, MTTP-388, MTTP Q95H, MTTP Q244E, and MTTP_rs2255119) were chosen to uniquely identify four of the eight haplotypes (see Table 2). Only two of the SNPs within HapMapII uniquely define a haplotype; we therefore estimate that using the additional SNPs here is as informative in terms of haplotype coverage, or even more so, than using only the five nonredundant ones within HapMapII.

We have recently reported an association between risk of nonfatal and fatal cardiovascular disease and MTTP genotypes. The MTTP-493T variant was associated with increased risk of cardiovascular disease in the WOSCOPS study, and this may reflect a survival effect by a lower allele frequency in a long-lived cohort. We speculated that the effect was mediated through myocardial vulnerability due to the strategically important effect of MTTP for lipid trans- port. However, the present study provides reliable evidence against any significant association of the MTTP gene with longevity.

ACKNOWLEDGMENTS

F. Karpe and D. C. Rubinsztein are Wellcome Trust Senior Clinical Research Fellows. The Oxford Healthy Aging Project received funding from the Medical Research Council, the Department of Health. and the Clothworkers’ Foundation.

The expert help of Jacqueline Birks is gratefully acknowledged. Dr. E. Zeggini, Wellcome Trust Centre for Human Genetics, Oxford, U. K., is thanked for valuable advice on statistical handling of the data.

Address correspondence to Fredrik Karpe, MD, OCDEM, Hospital, Oxford OX3 7LJ, U.K. E-mail: Fredrik.Karpe@ocdem.ox.ac.uk

Ashford JW. APOE genotype effects on Alzheimer’s disease onset and epidemiology. J Mol Neurosci.

;

:

–

Kamboh MI. Molecular genetics of late-onset Alzheimer’s disease. Ann Hum Genet.

;

:

–

Wilson PW, Schaefer EJ, Larson MG, Ordovas JM. Apolipoprotein E alleles and risk of coronary disease. A meta-analysis. Arterioscler Thromb Vasc Biol.

;

:

–

Decision Editor: Luigi Ferrucci, MD, PhD