Experimental Gerontology 36 (2001) 1303-1315 ——<—<——$—<——www.elsevier.com/locate/expgero

exhibit sex-dependent influence  human Jon gevity

Department ¢ t of | f Thrombosis | ee EEE ISS SOP: Research, | POPE EARLE ESE SA, University ¢ pp) of Southern 1 1 Denmark « cand | ET1 Department « t of ( f Clinical Biochemistry, | , Ribe ¢ EN EOE> County | OS ees» Hospital i lin | 1 Esbjerg, | ON REE TAS, Denmark “Epidemiology, 1 , Institute ¢ 2 of | f Public } > Health, « , and # oP1 Aging I Oe OO> Research ( eet idi Center, PE, University ¢ y of s Southern 1 1 Denmark-Odense BE PAE EINE EROSUniversity, | , Denmark

Received ¢ , } January 4 -../0 ; received i lint | revised { | form - . March % -../0 ; accepted ¢ 1 ) March * -../



with « 1 cardiovascular « “oner disease < > and | EE ED III TE| longevity i  1 the I > Danish | reyes bree1 population. ,  . New | REED IEE Ee; procedure > that « t combines  both | | demographic | and | | the | — eI- individual | vanyooeeeegenetic | EN EEE OEE EME- information | eein NE EEE| determining | reethe | relative |    of | the observed | ee epee| genetic variations |   _———s—— &; applied. ’ oN_ The : - sex-dependent i  influences  1can | | be |  found | | by introducing eesex-specific | - population : REEDED OE| survival | ‘Pre.’| and | “Ne KN ON| incorporating | the 1   of | " gene-sex | _ interaction. “soneThree | ee iO- genetic eee pie PMPspolymorphisms, ; . angiotensinogen | "6(cid:26)-,7(cid:27) reeceblood | ‘oe he orn| coagulation | ©. eee| factor  VII 89(cid:1)(cid:29)(cid:29): (6(cid:25),7, c~v™ &*and | ee| FVII- ,-,(cid:4)(cid:7)(cid:8)/.(cid:27) DLL DYELD DS 9 ODDS_ manifes  NEN ENEignificant |  See NE eainfluences |  on | ee OS| survival | oonint | males, ' with | sae eran| reduced | neh OMEN| hazards | of death : | for carriers ¢ s of t f the « eee EE”> angiotensinogen | "-,7 ) allele, t , the ] 9 7 VII ( (cid:25),7, allele, < , and t I the J 9(cid:1)(cid:29)(cid:29)(cid:20),-,&/. ) allele. ' . The results : ; show a AMSthat : oet some ¢ of 1 eon eethese | > genotypes ¢ ociated 1  <n| with | | lower 1 “risk « of | *(cid:1)3 ) could ; | also 1 » reduce t : the carrier’s ¢ s death 1 1rate é > and ¢ OME REINO OES”| contribute t >to] ANT Ne Rens» longevity. I . However, t , the | > presence « > of s f sex-dependent ¢ t effects < sand t 1 the fact t t that 1 t major t CVD-associated § | genes { Mow Naty:: failed t Io| to i ) impose ¢ ae eee”- detrimental i | influence « >on | | longevity | lead lus 1 ; to concur t “Beer that t eyet the < > aging | , proces    “oos highly « a ENE ERNE EEE/ complicated. ¢ pee -../ | Elsevier r Science | > Inc. : aMAlli >wrest **| rights 1 s reserved.

Keywords: ¢ : Gene; |  ; Cardiovascular « r disease; § ; Sex-dependent i t influence; |  ; Longevity;  ; Survival ¢ | analysis

 , Introduction

polymorphisms « ON | 1a ew eee| variety | of |  shave | - been : | studied | | to ) see | if | * they « ‘are | - associated | | with

Corresponding <  : author. 7 . Tel.: - (cid:1)DE(cid:20),F/(cid:20)-.F(cid:20)//.10 ; fax: (cid:1)DE(cid:20),F/(cid:20)-.F(cid:20)//1E(cid:30) OrE-mail « EEE ON| address: \ : yashin@demogr.mpg.de ( (AL . Yashin).

.7,/(cid:20)77176./6C  see | > front 1 t matter  -../ | Elsevier r Science | > Inc. 4 . All | rights 1 s reserved. &(cid:29)(cid:29)? >.7,/(cid:20)77178./:../.-(cid:20)D

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3H(cid:28) \ polymorphism « 1 of ( *(cid:1)3 ) candidate ¢ > genes. 1 . Table 1 > revised f 1 from I 1 Bladbjerg « z et z tal. ( 8/EEE: F-?//..(cid:20)7(cid:30) . FVIE t : blood NEE ND EEScoagulation { ne es1 factor r VII; | &(cid:28)(cid:29)? CEE IDOE NEEDS: plasminogen <  | activator i r inhibitor-1; t ; t-PA: t   MORNE AAAS NE> plasminogen : | activator; ¢ ; GPITb/Ila: “eoplatelet 1 t receptor § men NRA ERAr glycoprotein | iD1 Tib/Ia; | “oN eee ee; prothrom: | : prothrombin; | "(cid:26)=9(? ok poe: methylene t a ON COLI> tetrahydrofolate 1 > reductase; (cid:28)*!? cee ae ee: angiotensin ¢ — a1 converting ¢ ne EES OEy enzyme; ¢ , pee; angiotens: EDI III IID IE: angiotensinogen

Genotypes Control §  | group Centenarian |  | group (cid:1)- , (p-value) NEnumber ( © Orr (frequency) number ( eh OE BPEr (frequency) Haemostasis § s genes FVIII (6(cid:25) ,7, .(cid:30)F-8.(cid:30)11: ((,7, /1-8.(cid:30)F/: /7J8.(cid:30)FD: ((cid:25),7, ,J8.(cid:30)/F: -F8.(cid:30)/7: (cid:25)(cid:25),7, -8.(cid:30)./: -8.(cid:30)./: <aFVII-323ins10 /(cid:30)7.8.(cid:30)DF: &.&. /718.(cid:30)JF: /7,8.(cid:30)F-: &.&/. D-8.(cid:30)-.: ,.8.(cid:30)/1: &/.&/. ,8.(cid:30).-: ,8.(cid:30).-: FVII i [ intron7 ( 8,J(cid:19)(cid:21): .(cid:30)..8.(cid:30)EE:  =7=7 .8.(cid:30)..: /8.(cid:30)..7: =7=1 /.8.(cid:30).7: 18.(cid:30).,: =7=J ,8.(cid:30).-: 18.(cid:30).,: =1=1 E18.(cid:30)DF: F18.(cid:30)DJ: =1=J J78.(cid:30),J: 1J8.(cid:30),J: =J=J /J8.(cid:30).E: /78.(cid:30).F: =J=F .8.(cid:30)..: /8.(cid:30)..7: Fibrinogen < D77@6(cid:28) .(cid:30)1,8.(cid:30)EE: D77@@ /,-8.(cid:30)11: /-E8.(cid:30)J.: D77@(cid:28) 1D8.(cid:30),-: 7,8.(cid:30)-F: D77(cid:28)(cid:28) D8.(cid:30).-: ,8.(cid:30).-: &(cid:28)(cid:29)(cid:20)1J78D@67@: -(cid:30)/78.(cid:30),D: D@D@ 778.(cid:30)-J: 7D8.(cid:30)-E: D@7@ /.18.(cid:30)7,: F18.(cid:30)D1: 7@7@ D.8.(cid:30)-.: DJ8.(cid:30)-7: tPA i . intron8ins311 /(cid:30)F78.(cid:30),E: Wl J18.(cid:30),F: J/8.(cid:30),E: (cid:29)63 ED8.(cid:30)DJ: J18.(cid:30)D/: 363 ,/8.(cid:30)/7: ,J8.(cid:30)-.: GPIIb/IIIa | A6&,, .(cid:30)-/8.(cid:30)E.: AA /D/8.(cid:30)J.: /,,8.(cid:30)J/: A& 7D8.(cid:30)-J: DE8.(cid:30)-1: && D8.(cid:30).-: 78.(cid:30).,: Prothrom ‘ -.-/.@6(cid:28) .(cid:30)FD8.(cid:30),1: @@ /E,8.(cid:30)EJ: /FD8.(cid:30)EF: @(cid:28) 18.(cid:30).,: ,8.(cid:30).-: AA . . "(cid:26)=9( (cid:28)6(cid:1)//D .(cid:30)1.8.(cid:30)JD: AA E18.(cid:30)DF: F78.(cid:30)D1: AV F18.(cid:30)D,: JE8.(cid:30)D,: VV /E8.(cid:30)/.: --8.(cid:30)/-: #& > regulating § y genes. (cid:28)*! Soe BN eee| intron! 6ins287 .(cid:30).J8.(cid:30)EJ: Wl D18.(cid:30)-,: D/8.(cid:30)--: (cid:29)63 /.-8.(cid:30)7/: E78.(cid:30)7/: