Table 2. Comparison of Genotype Distribution of Eight SNPs Between Higher and Lower Age Groups

Distribution* Distribution* SNP Genotype ,57 years (cid:2)57 years p Male Female p IL-10 (cid:1)819 C/C 26 (10.6) 22 (8.6) 25 (9.9) 23 (9.3) T/C 125 (51.0) 101 (39.6) 112 (44.5) 114 (45.9) T/T 94 (38.4) 132 (51.8) .0026y 115 (45.6) 111 (44.8) .8438y TNF-a (cid:1)1031 C/C 11 (4.5) 6 (2.4) 7 (2.8) 10 (4.0) T/C 67 (27.3) 56 (21.9) 69 (27.4) 54 (21.8) T/T 167 (68.2) 193 (75.7) .0611 176 (69.8) 184 (74.2) .2785 IL-1b (cid:1)511 T/T 49 (20.0) 53 (20.8) 53 (21.0) 49 (19.8) C/T 131 (53.5) 121 (47.4) 126 (50.0) 126 (50.8) C/C 65 (26.5) 81 (31.8) .1982 73 (29.0) 73 (29.4) .9085 IL-6 (cid:1)634 G/G 17 (6.9) 12 (4.7) 16 (6.3) 13 (5.2) C/G 85 (34.7) 89 (34.9) 92 (36.5) 82 (33.1) C/C 143 (58.4) 154 (60.4) .6449 144 (57.2) 153 (61.7) .3002 IL-18 (cid:1)607 C/C 33 (13.5) 33 (13.0) 33 (13.1) 33 (13.3) A/C 126 (51.4) 125 (49.0) 116 (46.0) 135 (54.4) A/A 86 (35.1) 97 (38.0) .4955 103 (40.9) 80 (32.3) .0456 TGF-b þ869 T/T 51 (20.8) 65 (25.5) 53 (21.0) 63 (25.4) C/T 121 (49.4) 124 (48.6) 131 (52.0) 114 (46.0) C/C 73 (29.8) 66 (25.9) .3288 68 (27.0) 71 (28.6) .6815 MMP-1 (cid:1)1607 1G/1G 18 (7.4) 27 (10.6) 25 (9.9) 20 (8.1) 1G/2G 125 (51.0) 106 (41.6) 111 (44.1) 120 (48.4) 2G/2G 102 (41.6) 122 (47.8) .1627 116 (46.0) 108 (43.5) .5766 MMP-3 (cid:1)1171 5A/5A 6 (2.4) 3 (1.2) 4 (1.6) 5 (2.0) 5A/6A 67 (27.4) 70 (27.4) 59 (23.4) 78 (31.5) 6A/6A 172 (70.2) 182 (71.4) .7739 189 (75.0) 165 (66.5) .0373

from http://biomedgerontology.oxfordjournals.org/ at McMaster University Library on March 25, 2015

yThe frequency of T/T genotype was compared to that of T/C and C/C genotypes. SNP ¼ single nucleotide polymorphism; IL ¼ interleukin; TNF ¼ tumor necrosis factor; TGF ¼ transforming growth factor; MMP ¼ matrix metalloproteinase.

The relation of the combination of IL-10 (cid:1)819 T/T and TNF-a (cid:1)1031 T/T with age was also evaluated by the chi- square test. A significant association of the combination of these two genotypes with age was observed ( p¼ .0145), but the association seemed to be weaker compared to the association of IL-10 (cid:1)819 T/T with age, suggesting that there was no additional advantage of the combination with TNF-a (cid:1)1031 T/T (data not shown).

gender with the genotype distribution of each SNP by a conventional chi-square test. As shown in Table 2, IL-10 (cid:1)819 T/C showed a significant association with age (p ¼ .0026). In addition, there was a weak association between gender and IL-18 (cid:1)607 A/C (p ¼ .0456) or MMP-3 (cid:1)1171 5A/6A ( p ¼ .0373), and a tendency of association between age and TNF-a (cid:1)1031 T/C ( p ¼ .0611).

The association of IL-10 (cid:1)819 T/T, IL-18 (cid:1)607 A/C, and MMP-3 (cid:1)1171 6A6A with age or gender remained significant after multivariate logistic regression analysis. The analysis also showed a significant association of TNF-a (cid:1)1031 T/T with age. OR and 95% CI are shown in Table 3. Consistent with the results in Table 2, the association of IL- 10 (cid:1)819 T/T with age showed the highest level of statistical significance (OR for an age interval for 1 year, 1.009; 95% CI, 1.002–1.016).

D ISCUSSION

In this study, we demonstrated that IL-10 (cid:1)819 T/C and (cid:1)592 A/C polymorphisms could be associated with aging in

Table 3. Logistic Regression Analysis

OR* 95% CI p IL-10 (cid:1)819 (T/T vs T/CþC/C) Age 1.009 1.002–1.016 .0099 Gender 1.161 0.814–1.657 .4105 TNF-a (cid:1)1031 (T/T vs T/CþC/C) Age 1.009 1.001–1.016 .0288 Gender 0.825 0.557–1.224 .3398 IL-18 (cid:1)607 (A/A vs A/CþC/C) Age 1.003 0.996–1.011 .3506 Gender 1.470 1.018–2.123 .0399 MMP-3 (cid:1)1171 (6A/6A vs 6A/5Aþ5A/5A) Age 1.002 0.995–1.010 .5935 Gender 1.520 1.030–2.243 .0351

To further evaluate the association of IL-10(cid:1)819 T/T with age, we divided our population into four groups (two decades each) as follows: 19–40 years, 41–60 years, 61–80 years, and 81–100 years, and the frequency of IL-10(cid:1)819 T/ T was compared among these 4 groups. As shown in Table 4, it was apparently increased in higher age groups (61–80 and 81–100) compared to lower age groups (19–40 and 41–60).

To investigate the relation of a previously reported IL-10 haplotype (22) consisting of (cid:1)1082 A/G, (cid:1)819 T/C, and (cid:1)592 A/C with age, we then genotyped IL-10 (cid:1)1082 A/G and (cid:1)592 A/C. As shown in Table 5, genotype distribution was completely consistent between IL-10 (cid:1)819 T/C and (cid:1)592 A/C, but (cid:1)1082 A/G showed a quite different distribution. There was no significant association of IL-10 (cid:1)1082 A/G with age (data not shown).

Notes: *OR for age indicates OR for an age interval for 1 year. OR ¼ odds ratio; CI ¼ confidence interval; IL ¼ interleukin; TNF ¼ tumor necrosis factor; MMP ¼ matrix metalloproteinase.

Table 4. Frequencies of Interleukin 10 (IL-10) (cid:1)819 T/T in Each Two Decades of 500 Participants Aged 19–100 Years

Table 5. Comparison of Genotype Distribution of Interleukin 10 (IL-10) Promoter Single Nucleotide Polymorphisms

Age (y) 19–40 41–60 61–80 81–100 IL-10 (cid:1)819 T/T 71/184 (38.6%) 26/66 (39.4%) 58/116 (50%) 71/134 (53%)

Genotype Number (%) IL-10 (cid:1)819 C/C 48 (9.6) C/T 226 (45.2) T/T 226 (45.2) IL-10 (cid:1)592 C/C 48 (9.6) C/A 226 (45.2) A/A 226 (45.2) IL-10 (cid:1)1082 G/G 3 (0.6) G/A 41 (8.2) A/A 456 (91.2)