- 874T i and - 1 +874A I . IFN-y < / allele   sin] 1 Italian « 1 centenarians ( ; (number « r of § F genes « ; examined { 1 for « reach § | group i ) is 1 s reported i 1 in t 1 brackets)

 Alls | subjects  Men   Controls Centenarians Controls Centenarians Controls Centenarians 9(cid:12)5  f subjects 248 ( 8(cid:15);1: 174 ( 8<(cid:15)(cid:13): ,=(cid:13) 8<,1: <. 81(cid:15): ;/ 8,(cid:13)/: ,(cid:15). 8.(cid:13)(cid:15):  - 874T /5(cid:15)1(cid:13) 8.<.: /5(cid:15)<(cid:14) 8,=.: /5(cid:15)1= 8,(cid:15)(cid:14): /5=<, 8<(cid:15): /5(cid:15)(cid:14). 8(cid:13)=: /5<=; 8,/.: +8 - 874A, /5=<. 8.1(cid:15): /5=1< 8,;1: /5=<= 8,1;: /5(cid:15)1; 8</: /5=.(cid:13) 8;=: /51(cid:15), 8,(cid:13).:

Significantly ¢ y different - t +874T -      \ allele ¢   vin ¢ 1 centenarian Vv 1 women V 1 with r 1 respect t t toc ) control v 1 women (    /(cid:1)/././1,(cid:4)(cid:1) 9(cid:12)   ewedifferences \ “ae; were ( - observed i lin t 1 the ¢ > distribution ¢ 1 of t F the t > two % ) alleles | s between 1 1 male « - and ee ENO ee1 female « - controls.

centenarian women than in control women 8(cid:20)   /5/././1,:(cid:30) whereas no significant difference APOwas Meeobserved -?in waite i ee eM SSdistribution teeof aha eethe two eeealleles between 1 | male « >and | | female « : controls. 1 Allele | - frequencies in centenarian men were not found IIEsignificantly different | from | | male « - controls.

(each) ) dNTP, ( /5= (cid:3)# | each : | specific | : primer | (antisense: Aen}TCA, ‘shen-ACA | Peg MeeAAg | “pee-CTg. ATA | ! (cid:16)! !(cid:1)0 noes’ Xue- sense » +874T: aNt*TTC’ fatTTA ( REM ASCAA ( !(cid:1)! > een te‘AAA, CAN.ATC | — Nt AD &‘AAA’ (cid:16)!(cid:16)0  MON kesense +874A: TTC TTA CAA !(cid:1)! AAA ATC AAA TCA), /5. J TaqGold (Perkin Elmer)—DNA poly- at Ao OMmerase, : =/ yng | aDNA t aeee Meee. template. ( . Cycling \ wi tO, WAS | —A Nee pe; performed at ‘ ;(cid:13) (cid:4)! ’ for ¢ 1 oo“,y min, | ,/ pee) cycles « sat ¢ ;1 (cid:4)! ee’ for: </ 7 pee) min, ¢ 1/ (cid:4)! “eefor ¢ (cid:15)/ ) min < . and * (cid:14). (cid:4)! vy’ for ¢ (cid:15)/ ) min ¢ 1 and 7 ./ ) cycles « > *sat ¢ ;1 (cid:4)! for </ ) min, =1 (cid:4)! for. (cid:15)/ ) min | and (cid:14). (cid:4)! for =/ ) min. The amplified products were monitored &(cid:21) electro- ae TEphoresis on  .K agarose gel EE IE ESDcontaining seeethidium reebromide | 8/5= ) we/mil).

4. , Discussion

_—eee emproduction of eee FYIFN-y &(cid:21) = peonatural killer 89N: aint)cells   sani 1 important 1 at role i ae>in |  FO1 bringing < r about < t acute i CO NE- inflam- reesemation. eetIn “peesthe subsequent PEE ED NE Oeantigen-specific phase of the immune aN eeresponse, IFN-y oNacts Peas  “aN peeregulator of antigen | ee eee| presentation mo. and | “asp eee| proliferation ; -and « eee| differentia- Oetion owof © eelymphocyte SN NEE NESpopulations. High-level produc- tion of ag eeIFN-y Sew TNduring this phase a =of oNhost in iadefence is now ¢ ee RANE”classically —_EN/ seen mo *1 aS < sal een pee1 hallmark « ‘of ¢ fat i type | , | reaction, characterized &(cid:21) activation of “aN EEA TNmacrophages and &(cid:21) strong | cellular FOinflammatory | EEN ETEreactions | r’s“owe oe| (Billiau | et cal., ,;;(cid:13):5

1$1 Statistical | | analysis

gene count ¢ t and ‘ . xX! . —eetables 1 > WETE | - constructed 1 | to « mey deter- oFmine | statistical | | significance | 8(cid:4). “analysis | - with | Yate’s correction) | of | ee' differences in. VA eee’allele “7 eeefrequency for | the IFN-y | 9> in | centenarians | -and « See Ie| controls.

3.1 , Results

et al. 8,;;;: ee EEE EEN EDdescribed   LE DOvariable length !(cid:1) repeat me RE NE Asequence | aA?in | - ™“N*.the | first | intron | of 1 * the | ~~ eeehuman | | IFN-y | “Pee/ gene —and showed that. allele M. is | associated with ahigh in vitro | ) IFN-y | / production. | In: 1 a ( | consecutive : study | DEE EEE’ (Awad et tal., ,;;;:(cid:30) ———e~, allele 7 M. . was f ; found t to | &(cid:3) se ee ye NE- associated | with MED ED A Aallograft | ee es- fibrosis | in lung | transplant | - patients, } -confirm- ing i its 1 role ; aS 5 al IE IIIS| marker ¢ of | BE LID TE‘high | eee BS| IFN-y | ND NEE/ production. | In:  AMme teefurther s study | / (Pravica ¢ Let i a =tal., 7 .///:(cid:30)   9>(cid:30) Tt “tO J   at the: =; ) end « welof t vanF the ¢ !(cid:1) ODrepeat 1 29 ee ADt region i in t 1 the { > first 1 ae EADSt intron « oOo1 of the MEAShuman IFN-y ae aNPsgene 8,(cid:13)(cid:14)(cid:15)+(cid:16)D(cid:1): was described, showing « an i “ae Em| absolute « swe Ka- correlation | mae AP Ne| between \ the | ONE ENN- presence of | F the oS  > re‘allele ; >and 1 | the | > presence « of t ‘the | I ON OE- high-producing microsatellite allele M.5 This  to  Oe OOpolymorphism

+874T -   SJrestoallowed assessment of conformation with the Hardy-Weinberg equilibrium for allele distribution both in MEELIS ES OMIcentenarian —and control popula- tion samples and no significant ee NEEDEDdifferences were NE OTobserved eein frequencies | moeof | "either | allele between the two groups of IIEsubjects (Table ,:5 In addition, the aoe eenfrequency of the a Jee+874T allele ase aSwas —— eecomparable to “=that. of | nA“the |  so-called. | allele : M. 8,. !(cid:1) eee eerepeats) | at | the microsatellite region in the a aefirst intron “PNof "the a“INF-y gene | - measured | | in | the | Italian | | population | | (Goris | et  ,;;;:5 . When | | the - analysis eee EE; WAS | Pere een; performed ; eee| according “eeer tO aaa pegender, t , the - >» +8747 eens PEallele 7 ree |> was | 7 pees; found | | less | ON EID; frequently >_™“rin

(cid:17)1 Lio ¢ ) et ¢ tal. / 7 / Experimental ( | Gerontology - $5 : ## ;