Fig. | /(cid:30) . The s > sex-specific s > survivals f s for « r angiotensinogen } " [ allele « > carriers sand 1 | non-carriers.

int . the « - original « | analysis 1 using 1 r the | » gene | - frequency 1 method | | (Bladbjerg « ret tal., /EEE:(cid:30) _ The | fact that | - the | Seegene | SLE J OE EOfrequency 1 EEE OO‘method 1 “om Ai| ignores | ape Re; interactions ' —— ao; when « EN IES ™™| comparing | “enerothe | 9 tA}gene | Cpe Be Eee: frequency EEE INS ESdifferences | nee Tee; between 1 new ye| the « ‘control | nn — ied| group ¢ y and 1 | the « - centenarians « ene es; could | en DLE| be ; 5m ON EN- attributed 1 | to 1 ) the | selack MAMof thw iho"efficiency | oeof yea"the iwgene PEER BENTfrequency ‘renamethod heewhen | Mw BRRapplied etto) aessmall | —e=FVn——samples. In | the aaJ“_™new model, the “Jrisk of ~ ome eet" gene—sex “pee J eeeinteraction is. defined “rras an | extra risk atfor ‘beremale carriers in ahem ey NAERcomparison to ~N Exeefemale carriers. Information from both sexes is used to determine the EEE TE IEE OEparameter of interaction. However, one important nontranditional epidemiologic ee eeapproach, t the « - case-only « "decidesign, | which “9 Maes| Was ¢ nee REEoriginally « derived | | for « ‘analysing | “Pee' gene-environ- “rr™*ment i “een ME NDt interaction i 1 in ¢ EE DINE| disease | ee mn Ne: prevalence ( NEE OE> (Piegorsch ¢ eedLet é i ital. /EED0 ; Khoury wey and | Me ON Ne| Flanders, | /EE1:(cid:27) can | | be | - introduced | | here to ~ Peweedetect | ENE NE DN ESS- gene-Sex | SN NEinteraction | aain | ——————e| human NP OEE_ longevity | When | ey Rh AMID| treating centenarians as | cases. | Taking “~"* &*the ne EN ENE SEangiotensinogen " allele for | aM NDexample, there  /.1 centenarian | carriers | 8,D 7 eee ™| males, ’ J- “eNO eee. females) ; senate) and ’ J1 ) non-carriers | 8/- oe TEmales, ¢ 1D | females) « ) of the : allele. ' _ The « meeeodds 1  Tatio « eR I ae oe) comparing (OLEANmale « oecarriers | tO | ) female « een aN ee eecarriers 1 is | -(cid:30)7/E ) with ¢ a | E7B confident interval of /(cid:30)-.,57(cid:30)-J1(cid:30) The statistical test showed  significantly higher proportion | of | "carriers | of | ‘the ; allele -   | male | - centenarians | than | that - in: eesfemale | meee J EE- centenarians 8(cid:1)-   7,FD(cid:27)    .(cid:30).-.: ) which | | means | that the ; allele | - favours | ; male : survival. . _ Although | | this NA eMconclusion is NM NRE EScompatible with our result, the case-only approach does not NEallow for evaluation | of |    ap eae- independent « effect |   ‘the | allele |    but 1 Preemerely » involves : a | departure from | | multiplicative « ~—Peeffects | ; (Rothman ; . and | | Greenland, /EEF0 Yang | ay oe- and | Khoury, /EEJ:(cid:30) In the 1 III TE> relative 1 poe> risk 1 ‘model « ew kieeoreee| exploited i lint 1 this | cer,s pap , OUT | LINED AASr primary 1 aM ARESinterest i omtis s not t only t ~ 7?/tot yo) test f an aet for t fe “aer the gene-—sex | interaction | oh NESE| but | ewalso | to DAE EIS EEEevaluate | the 1 ee Berisk | eeeof | eee‘the ; Joeallele « - OF OD LDgenotype : i» aS | well ; as | its  initial | | frequency. | In« . addition, ' 2(cid:15) > Can « also ¢ ) estimate 1 the » genotype we eeespecific “JN Seo> survival « | distribu- tion ; | as | eee; shown | in|   /(cid:30) _ Nevertheless, 1 the «   easil    ‘applicable « vee P= Spee- case-only  - approach | Lis ¢ al  _ useful tool for ean =)measuring > ee Neegene—sex BRN ENN BESinteraction in ee) SPRhuman longevity as a dSit “revs.avoids the troubles originated | from | Pee oN| ordinary « case-control « design.

(a) 1.0 0.9 obs. est. 0.8 0.7 0.6 0.5 (b) 0.8 obs. est. 0.7 0.6 0.5 0.4 0.3 20 40 60 80 100 )x(p)x(p

-(cid:30) . The « » observed ¢ | and « | estimated | | proportions ¢ sof « ' angiotensinogen | " [ allele « - carriers | : by rage | - for 1 ‘males ( 8(cid:2): 8(cid:19):(cid:30)

unexpected : | as | ; previous ; ; studies | shave : found : | sex-dependent « t effects « of t these | - polymorphisms on ¢ ope1. other | oo EEE ree‘ phenotypical t | traits. ] . For « ‘example, t , the § ee ees> genotypes ¢ sof t F the NDE IND ONE IIE IO- angiotensinogen § EOI| gene | > were found 1 ae” E| to | reebe NE EE OE EEE- significantl  ‘associated \ meee ye 9| with | oe oem| variation | eIin: ree Sa| systolic 1 ooresting | ELIE: (Hegele : nn —et i tal., /EED: and « | exercise ( Od> (Rankinen « ‘eo1 et é tal., : -...: ) blood | | pressure, | es, but «  int een IS ON| males. '  . The 1 _——results i wD OE; indicate that | t the | Ce NEN NEN» genetic \ : variation i in t \ the | NElocus 1 NE PO; modifies 1 the 1 ON NEE J OE OIE; responsiveness ( ; of t F the | - blood | | pressure 1 to EEN NIN Eeendurance 1 training, | but | the | - functional | | impact i Lis 1 va eeerelated 1 | to differences |   | SEX.” re_ The | - gender- related effect a =in Soethe genetic III TEmodulation of FVII plasma levels has been oestudied

+, . Tan ¢ 1 et ¢ tal. / - / Experimental ( | Gerontology - ./ 012234 3.2.53.36