the sample groups, with these repertoires displaying a marginally higher frequency in the aged subset relative to the controls (37 and 32%, respectively).

A comparison of the frequency of individual KIR gene repertoires within the aged subset and control group failed to reveal a statistically significant level of genotypic variation between the two samples groups. Interestingly, several KIR genotypes displayed notable differences in frequency when the aged and control cohorts were segregated according to gender (Table 4). In the aged males, the frequency of genotype 3/9 was considerably reduced in comparison to the young male controls (7 vs 27%). Similarly, a marked decline in the frequency of genotype 1 was apparent in the aged females compared to the young female controls (25 vs 41%). However, due to the limited number of males and females within each sample group, acceptable statistical analysis could not be performed on these data.

Analysis of the frequency of each KIR gene in the complete aged and control subsets revealed that all KIR gene frequencies were comparable in both sample groups, with the exception of KIR2DS3 and KIR2DL5. The frequencies of both of these KIR genes were significantly increased in the aged subset compared to the young controls (KIR2DS3, 41 vs 25%, uncorrected p-value 0.02, and KIR2DL5, 59 vs 45%, uncorrected p-value 0.03). Interest- ingly, the KIR gene frequencies of the young controls were similar to data previously obtained for a healthy Irish control group ðn ¼ 512Þ (data not shown), reflecting a true increase in KIR2DS3 and 2DL5 frequency in the aged sample group. When KIR gene frequencies were analysed with respect to gender, both the KIR2DS3 and KIR2DL5 genes displayed an increased frequency in aged males

To further analyse these results, the frequency of each of the KIR genes/pseudogenes were examined in the aged and control sample cohorts to assess whether a particular KIR gene may influence longevity within the Irish population. The frequency of each of the KIR genes within the aged and control sample groups are displayed in Table 5. Each of the currently known KIR genes were detected during this study

L.D. Maxwell et al. / Experimental Gerontology 39 (2004) 1223–1232

Table 4

KIR genotype frequencies observed in the aged and control subsets

Genotype # Aged ðn ¼ 93Þ Controls ðn ¼ 100Þ Male n ¼ 28 (%) Female n ¼ 65 (%) Total (%) Male n ¼ 41 (%) Female n ¼ 59 (%) Total 1 8 (29) 16 (25) 24 (26) 11 (27) 24 (41) 35 (35) 2 4 (14) 10 (15) 14 (15) 1 (2) 9 (15) 10 (10) 3/9 2 (7) 9 (14) 11 (12) 11 (27) 6 (10) 17 (17) 4 5 (18) 5 (8) 10 (11) 2 (5) 4 (7) 6 (6) 5/10 1 (4) 2 (3) 3 (3) 4 (10) 1 (2) 5 (5) 6 – 2 (3) 2 (2) – 2 (3) 2 (2) 7 2 (7) 1 (2) 3 (3) 1 (2) 2 (3) 3 (3) 7a – 1 (2) 1 (1) 1 (2) 2 (3) 3 (3) 8 1 (4) 8 (12) 9 (10) 3 (7) 2 (3) 5 (5) 11 – – – 1 (2) 1 (2) 2 (2) 12/17 1 (4) 2 (3) 3 (3) – 1 (2) 1 (1) 13 1 (4) 1 (2) 2 (2) 1 (2) – 1 (1) 15 – 3 (5) 3 (3) 1 (2) 1 (2) 2 (2) 19 – – – – 1 (2) 1 (1) 20 – 1 (2) 1 (1) – – – 22 – – – – 1 (2) 1 (1) 23 – – – 1 (2) 1 (2) 1 (1) 24 1 (4) 1 (2) 2 (2) 2 (5) – – 27 – 1 (2) 1 (1) 1 (2) – – 28 1 (4) – 1 (1) – – – 29 1 (4) – 1 (1) – – – 30 – 1 (2) 1 (1) – – – 31 – 1 (2) 1 (1) – – – 32 – – – – 1 (2) 1 (1)

were examined for determination of the KIR2DS3 and KIR2DL5 frequencies (Table 6). In contrast to the initial result, both the KIR2DS3 and KIR2DL5 frequencies observed within the second aged subset were comparable to that of the second group of young controls (KIR2DS3, 21 vs 25% and KIR2DL5, 40 vs 45%). Hence, the significant increase in the frequencies of these two genes that was detected in the first cohort of elderly subjects, was subsequently lost. When the KIR2DS3 and KIR2DL5 frequencies for both subsets of aged and control samples

and females relative to young controls of the same gender, indicating no association with gender. Interestingly, only the KIR2DS2 and KIR2DL2 genes displayed gender- specific variations in frequency—the frequency of both these KIR genes were increased in the aged females relative to young female controls (55 vs 37%).

In an attempt to confirm the significance of the increase in the KIR2DS3 and KIR2DL5 frequencies in the aged cohort relative to the young controls, a cohort of healthy aged subjects and control samples

Table 5

The KIR gene frequencies observed in the first group of aged and control

KIR gene Aged ðn ¼ 93Þ Controls ðn ¼ 100Þ Male n ¼ 28 (%) Female n ¼ 65 (%) Total (%) Male n ¼ 41 (%) Female n ¼ 59 (%) Total (%) 2DL1, 2DP1 26 (93) 62 (95) 88 (95) 40 (98) 57 (97) 97 (97) 2DL2 16 (57) 36 (55) 52 (56) 27 (66) 22 (37) 49 (49) 2DL3 24 (86) 58 (89) 82 (88) 36 (88) 57 (97) 93 (93) 2DS1 11 (39) 31 (48) 42 (45) 15 (37) 21 (36) 36 (36) 2DS2 16 (57) 36 (55) 52 (56) 27 (66) 22 (37) 49 (49) 2DS3 12 (43) 26 (40) 38 (41)* 12 (29) 13 (22) 25 (25)* 2DS4 28 (100) 60 (92) 88 (95) 38 (93) 56 (95) 94 (94) 2DS5 7 (25) 25 (38) 32 (34) 12 (29) 16 (27) 28 (28) 3DS1 11 (39) 31 (48) 42 (45) 16 (39) 23 (39) 39 (39) 3DL1 27 (96) 60 (92) 87 (94) 38 (93) 56 (95) 94 (94) 2DL5 17 (61) 38 (58) 55 (59)** 18 (44) 27 (46) 45 2DL4, 3DL2, 3DL3, 3DP1 28 (100) 65 (100) 93 (100) 41 (100) 59 (100) 100 (100)

*Uncorrected p-value 0.02; **uncorrected p-value 0.03.

L.D. Maxwell et al. / Experimental Gerontology 39 (2004) 1223–1232

the possibility of a KIR genotype with a potentially important role in healthy ageing, being masked by the array of other genotypes encountered.

Table 6

KIR2DS3 and KIR2DL5 frequencies of subsets of aged and control samples

First group Aged n ¼ 93 (%) Controls n ¼ 100 (%) 2DS3 38 (41)* 25 (25)* 2DL5 55 (59)** 45 (45)** Second group Aged n ¼ 89 (%) Controls n ¼ 89 (%) 2DS3 19 (21) 21 (24) 2DL5 36 (40) 39 (44) Total group Aged n ¼ 182 (%) Controls n ¼ 189 (%) 2DS3 57 (31) 46 (24) 2DL5 91 (50) 84 (44)