_ Results

Genotypic and allelic data relevant to INS-FokI-RFLP and IGF2-AvalI-RFLP are shown i oe |.in’ Jee oom1 Tables SL -and 7 (cid:30)& , respectively. All t | the s > sample | > groups | ; were I >in] (cid:22)-=! :(cid:11) ) significant difference   oe GRR Ryobserved ae penebetween. NT IE DN OEEsex-matched | eee EMEcentenarians | and | younger NN ESindividuals | or between age-matched males | and females. | The results (cid:11)* NE“linkage DEE LEE EEdisequilibrium studies between  (cid:11)* markers are reported in Table /& where ao MeeeHUMTHO1 data *(cid:21)(cid:11)" the previous | | study 6$(cid:2) ; Benedictis | et i (cid:17)(cid:10)!& (cid:31)3327 ) are | awalso | ao NN. considered. ' The « disequilibrium» | Was rtnot | NN EDsignificant co leerbetween INS" and RDN A| IGF2 | ANF OOmarkers, while | it was | highly | eeesignificant between each « (cid:11)* these 1 - markers and 1 | the | - HUMTHO1 : “NODshort « > wre.or | ‘long j alleles. | oeIni the | oelight (cid:11)* * the 1 results found using the relative-risk approach (Tan et (cid:17)(cid:10)!& (cid:30)00(cid:31)7& we mee NN Oedecided to look at the ENE DDI IIEassociation o Me™ aebetween. each (cid:11)* ™~ “bE"the ‘pee XAdiallelic markers raeg eMand Me Tg NNNspecific HUMTHO1 alleles. The results » are | : shown | in’ | Tables - D(cid:23)A! In -each (cid:11)* “the | : sample | negroups, | the | : global « | disequilibrium values” were | statistically significant |  <I 0(cid:1)000(cid:31)(cid:3)(cid:1) ne iExact meertests ees &/ were ou“then | aeapplied to. | SCX- matched control/case- eee Eecategories to a)verify the Ma EFnull hypothesis (cid:11)* EINE OEE POhomogeneity between haplotypic frequency oedistributions. eee SDThe adistribution (cid:11)* TH-INS NOhaplotypes was not

Table /

Values ¢ (cid:11)* f linkage ¢ > disequilibrium | 1 between | 1 pairs « (cid:11)* f markers i sin 2 (cid:30)0(cid:23)A0 ) year « r old s 1 subjects sand i 1 in ¢ 1 centenarians. I . Data relevant t tto’ » THY Corer reese1 polymorphism z rare f *(cid:21)(cid:11)" $(cid:2) pee NE EN> Benedictis e set 2 tal. ( 6(cid:31)3327 6(cid:22)E#(cid:20)(cid:22)0(cid:31) Poe ene| alleles r recoded a  Jas s s small 2 land 1 large)

 Males ( s(n =    - 119) Females (    (cid:31)/A(cid:3) TH-INS TH-IGF2 INS-IGF2 TH-INS TH-IGF2 INS-IGF2 (cid:30)0(cid:23)A0 ) year « r old s | subjects  0!02/ 0!(cid:31)0(cid:30) 0!0(cid:31)(cid:30) 0!02/ 0!033  0!00(cid:31)  0!02/ 0!(cid:31)A3 0!(cid:31)0(cid:30) 0!03/ 0!(cid:31)2D  0!0 / "(cid:17)(cid:3)6"(cid:8)(cid:12)7  (cid:31)00!0F A!0F (cid:31)(cid:31)!A@F 23!(cid:30)F /!2F (cid:31)!3F Det rel 6(cid:31) (cid:18)*7 25 ! (cid:30)2 (cid:30)(cid:30)!@// 0! @D 6(cid:12)(cid:5)7 (cid:30)A!3@@ (cid:30)D!2@(cid:30) 0!00 6(cid:12)(cid:5)7 Males ( s(n =  -72) Females ( 3 (n   (cid:31)DA(cid:3) Centenarians  0!03 0!03D  0!00D 0!030 0!(cid:31)(cid:30)0  0!00(cid:30)  0!03 0!(cid:31)3  0!0DD 0!(cid:31)00 0!(cid:31)2(cid:30)  0!0A@ "(cid:17)(cid:3)6"(cid:8)(cid:12)7  (cid:31)00F D2!(cid:30)F 3!(cid:31)F 30F @ !3F (cid:30)!@F Deel rel 6(cid:31) (cid:18)*7 (cid:30)/!(cid:31)(cid:31)0 (cid:31)/!/D/ 0!0DA 6(cid:12)(cid:5)7 (cid:30)3!D2(cid:30) /@! 20 0!003 6(cid:12)(cid:5)7

significantly - different | between. centenarians and | controls in females |    0(cid:1)032(cid:3)(cid:2) while IIIsignificantly | different in females"   = ( 0.031). <(cid:12) the contrary, | the | NI Madistribution | (cid:11)*  TH- CoeIGF2 pe EEE J LLINhaplotypes | Was | I NELLIE EN IPsignificantly | Meedifferent ase Meee SAbetween | NMED. J BOEcentenarians | and | | controls - in males    —~ ape0.002), Jreeomwhile 1 Te IEE POS- non-significantly « different 1 in | | females (     0.130). | Interestingly, , when III III OD OID III J PIII NINA IID IID INABIISID ISDE DN FEB IF III NII IIA ED J NN DINEthe haplotypic frequency distributions were compared between male and female centenarians,

Table - D

TH-STR/INS-FokI | I linkage c 2 disequilibrium a 1 analysis ( 6(cid:1)7 )inr 1 males. 1 . TH-STR a alleles 2 are i  > indicated a Jas € @& 3& 2&3&(cid:31)0(cid:1)& (cid:31)0& according t to | the 1 NE DANII ESrepeat | ‘oenumber. nnn10° |   the ED OED NEA BOS: imperfect | - HUMTHO! : allele (cid:31)0 ) (Puers « et j (cid:17)(cid:10)!& (cid:31)33/7! >B9 ’ indicate eee EE ONSENabsence/presence « (cid:11)* f the 1 > restriction s 1 site. ] oN ee. Haplotypic 1 > frequencies ¢ ; estimated | am NNI by! «<a; Maximum | Cee AA AP EM1 Likelihood ( 6#%=7 ) and ONIN ESexpected ( 6=I97 ) under t r the 1 > null | | hypothesis J ; D = joan) = ( 0

Haplotype (cid:30)0(cid:23)A0  ) year ¢  r old s | subjects ( s(n =   (cid:31)/A(cid:3) (cid:31)00(cid:23)(cid:31)03  ) year ¢  r old s | subjects (    (cid:31)DA(cid:3) #%= =I9  #%= =I9  @> 0!(cid:30)@(cid:31)  0.221  0!0D0 0!/(cid:31)/ 0!(cid:30)@A  0!0D@ @9 0!000 0!0D0 —( 0!0D0 0!000 0!0D@  0!0D@ A> 0!(cid:31)D@ 0!(cid:31)(cid:30)2  0!0(cid:31)2 0!(cid:31)3D 0!(cid:31)@@  0!0(cid:30)2 A9 0!00 0!0(cid:30)/ —( 0!0(cid:31)2 0!000 0!0(cid:30)2  0!0(cid:30)2 2> 0!(cid:31)// 0!(cid:31)(cid:31)D  0!0(cid:31)3 0!(cid:31)@0 0!(cid:31)/@  0!0(cid:30)D 29 0!000 0!0(cid:31)3 —( 0!0(cid:31)3 0!000 0!0(cid:30)D  0!0(cid:30)D 3> 0!(cid:30)/(cid:31) 0!(cid:31)3@  0!0/ 0!(cid:31)D@ 0!(cid:31)(cid:30)  0!0(cid:30)(cid:31) 39 0!000 0!0/  0!0/ 0!000 0!0(cid:30)(cid:31) —( 0!0(cid:30)(cid:31) (cid:31)0(cid:1)> 0!0D/ 0!(cid:31)@(cid:31)  0!(cid:31)(cid:31)2 0!0D(cid:30) 0!(cid:31)@0  0!(cid:31)(cid:31)2 (cid:31)0(cid:1)9 0!(cid:31)DA 0!0(cid:30)3  0!(cid:31)(cid:31)2 0!(cid:31)D 0!0(cid:30)A  0!(cid:31)(cid:31)2 (cid:31)0> 0!0/D 0!0(cid:30)3  0!00 0!000 0!000  (cid:31)09 0!000 0!00 —( 0!00 0!000 0!000  Total (cid:31)!000 (cid:31)!000 0!000 (cid:31)!000 (cid:31)!000 0!000

(cid:31)@@2

Table