The frequency of HLA antigens is largely dependent upon the geographic location of the study population (Caruso et al., 2000, 2001). In this study, the homo- geneous nature of the population from the north of Ireland, coupled with low levels of immigration due to the regions troubled past, has helped to alleviate some of the potential bias. The extremely polymorphic nature of the HLA complex creates a diverse range of haplotypes, thus lowering the power of the subsequent statistical analysis. Major limitations in the studies reported to date are the number of aged individuals available, and complete background histories of health or ethnicity for study participants. It is proposed that HLA haplotype frequencies are often affected by environmental deter- minants such as a famine or an epidemic (Izaks et al., 2000). The evidence accumulated to date would suggest that there are a number of gender-specific HLA haplotypes associated with successful ageing in different geographic regions. To fully elucidate the role of the HLA in longevity broad studies need to be performed integrating the many HLA typing laboratories through-

In recent times, a plethora of studies have been performed in an attempt to fully resolve the role polymorphism of the HLA has in longevity. However, to date, a large body of conflicting data has been amassed (Caruso et al., 2000, 2001). The present study set out to specifically confirm the previously reported increase in the frequency of the HLA-A1, -B8, -DR3 haplotype (22.9 vs 8.7%) in aged males of the northern Irish population (Rea and Middleton, 1994).

Table

The observed frequencies of the most common HLA and TNF polymorphic haplotypes in the healthy aged individuals and the young controls

Total HLA-A HLA-B HLA-DRB1 TNF-a TNF-b Controls n(cid:5)100 (%) Aged n(cid:5)93 (%) / / 1 8 3 A G 12.8 11.3 3 7 15 G A 7.3 5.4 2 44 4 G A 6 zero Males HLA-A HLA-B HLA-DRB1 TNF-a TNF-b Controls n(cid:5)41 (%) Aged n(cid:5)28 (%) / / 3 7 15 G A 8.5 8.9 1 8 3 A G 6.1 7.1 2 44 4 G A 3.7 1.8 2 44 7 G G 4.9 Females HLA-A HLA-B HLA-DRB1 TNF-a TNF-b Controls n(cid:5)59 (%) Aged n(cid:5)65 (%) / / 1 8 3 A G 17.8 13.1 3 7 15 G A 6.8 3.9 2 44 4 G A 5.8 zero 29 44 7 G A 5.1  /

The observed allele and genotype frequencies for the two polymorphic markers of the TNF genes

Controls n(cid:5)100 Aged n(cid:5)93 / / Male n(cid:5)41 (%) Female n(cid:5)59 (%) Total (%) Male n(cid:5)28 (%) Female n(cid:5)65 (%) Total (%) / / / / TNF-a AA 2 (5) 5 (8) 7 (7) 1 (4) 7 (11) 8 (9) AG 11 (27) 21 (36) 32 (32) 9 (32) 22 (34) 31 (33) GG 28 (68) 33 (56) 61 (61) 18 (64) 36 (55) 54 (58) A 15 (18) 31 (26) 46 (23) 11 (20) 36 (28) 47 (25) G 67 (82) 87 (74) 154 (77) 45 (80) 94 (72) 139 (75) TNF-b AA 18 (44) 18 (31) 11 (36) 11 (39) 25 (38) 36 (39) AG 18 (44) 33 (56) 51 (51) 12 (43) 28 (43) 40 (43) GG 5 (12) 8 (14) 13 (13) 5 (18) 12 (18) 17 (18) A 54 (66) 69 (58) 123 (61) 34 (61) 78 (60) 112 (60) G 28 (34) 49 (42) 77 (39) 22 (39) 52 (40) 74 (40)

Acknowledgements

out Europe to increase the number of aged samples and provide a strong foundation for meta-analysis.

The high degree of polymorphism within the HLA region creates an opportunity where a unique immuno- logical profile can be generated for individuals. This study attempted to widen the scope of HLA association studies by including polymorphism located in the class III region. Many class III genes have the potential to modulate immune function such as, com- plement proteins and the heat shock proteins and it is important to consider the effects that polymorphism of these genes may have during immunosenescence. The formation of immunogenetic profiles for successfully aged individuals incorporating such parameters as HLA haplotypes and cytokine gene polymorphism profiles will contribute to a resolution of the underlying molecular mechanisms occurring during immunosenes- cence.

The authors wish to acknowledge The European Union for support under the aegis of European Union Concerted Action on the Molecular Biology of Immu- nosenescence (EUCAMBIS; Biomed 1 contract CT94- 1209); and Immunology and Ageing in Europe (IMA- GINE; QLK6-CT-1999-O2031). OA Ross was a recipi- ent of a CAST Award jointly funded by the Department of Education and Learning (Northern Ireland) and the Histocompatibility and Immunogenetics Charitable Trust Fund.

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