Figure 1 shows the linkage disequilibrium between the single nucleotides (SNPs) in the microsomal triglyceride transfer protein (MTTP) gene typed to estimate the haplotype frequencies in the old population and the control population. Using the chosen SNPs against those within the HapMapII database, it is concluded that, of the 14 SNPs genotyped in the younger population, 7 were identifiable within HapMapII (MTTP-1428, MTTP-164, MTTP D98E, MTTP I128T, MTTP S166N, MTTP H297Q, and MTTP_rs881980). Of these seven SNPs, there were two pairs in complete LD. The SNPs used in this study were identified primarily from previous publications in which MTTP haplotypes have been studied, not from data within the HapMapII Project. Comparing the haplotype coverage across the MTTP region (Table 2), 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.

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 transport. 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. Email: Fredrik.Karpe@ocdem.I'm sorry, but there is no text enclosed in ``` ``` to be processed. Please provide the text you want me to proofread and improve.