- Email: [email protected]
L006 Association of angiotensin converting enzyme gene polymorphism with carotid arterial wall thickness
A
1
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1 N 9 4 PH
2
9
-
8
A
BLGDDFRESSURE HESITAB~OFBLGODFRES8UREAND A3mrcAN DE2ERM3NANR3 fNHYPERTEHs3wmYaLrFrDEMtc AWCmvIcy, CEGrim*, TAKotchen*, m@mrcANs.= PHanret*, HJaeob,JhfKotchm,RRomatLMe&alc of
WiscOrrs@ Milwaukee, WI. AflkatrArrre4iearu (AA)havca b i g Tlrepurpoaaofthis rcportisto a n d d( c ia C r Ofrnetabcdic, rezkal, and dedcribc evidmceforbsritabitity o i 4f A Cardiovasdardctemkm orcorrcfatea sibpairs(SSS18-55years),withesehsib havingbotbhyprtarsion m andSCrtU2t CbOtSStSfOl >200ttrgAU. Basedon24-bmrr ” padentbtood p p
m w
( As
i a s ev b oy d c sd te associated s d with o sACEJ/Dpolymorphism. t i rt s a au Ini this o study, as o z r 142rnrrdfsand86tnmH& K+ectkdy. Meaobodya$ f a r IMTwasdefinedasthemeanof IM’fmeasurements at 12
m h
m a w . =a s r in 0 r observed istribgsib-aibcodadeowas g u n for t 1
c
-
m er 2 a e awakediastolicbloodp p 0 butnotforawakc Systokbloodtrn=w . = 1 0 Signi6earrt sib-sibeomdationswereab?o obsefvcdlbr:bodysurfacc amaandbodySrrase iraiex;Skirrfdd dkkncssmmssuedateaveral renalbloodflOW sites;fkstingbloodghtwscandHDLchok@emi; (PAHCI earancc)bebre,atrdinsespenscto gradsdirttiisiorrs of 220rcPinct2hrir3e (-w; S1-arfittrrrtion rata(iaulirrckrancc)in “ mmmmnK@ Oftdvmtricutsr ~~w ~ diastoleard massandM Vsrrt2ieutar internaldianwendurisrg tmtybcthe duringsystolc.Thus,inAAj.sIcepiqbtoedpre=uras mostreliableblocdpresaura pbmotyps&wwaktingtwitabilityof hypcneasion. Haritabtsattcmtions ofrmalihnctiq ghrcoaeand fipidmctabob “m andheartsiznsaycOrltZibute totbehigh prcvsdemce ofhypcrtsesioe andhypsrtmsive CVDinM. (
W
O O
studieshave determinedwhethercwotid artery intima media thickness (MT) in aaymptomaticsubjects is
o r rm
P 0
A r
~
c
h
t
lr
ut o e -
sites of the carotidarteriesusing B-modeultrasound. ACEI/Dpolymorphism o kwas determined s in 355 healthy D r e men(54*7years)recruitedfrom adsurveyof rk 3 / e g t / a random m l d D sample of Southern Europe. The ACE genotype equilibrium[DD, r distribution l was in Hardy-Weinberg e s o 135(38%}ID, 150(42%);II, 70 (20%)].None ofa the e 7 ) ds cr t 0 kr n e . ai d 1 me4r v recognizedriskfactors[age,smokinghistory(21%were i current smokers), f l blood pressure i c c84+10 a s \137k16, 0 vbodymassindex(2fxt4kg/m), r s u diabetes(6%), eu t r r s s mmHg), 0 3 fasting plasma. glucose level5 (5.94*1.18 rmnrWL), 2 ) fasting plasma total cholesterol level (6.02i0.98 mmol/L),LDLcholesterollevel (3.85M195mrrroUL), triglyceride level (1.45ti.99 mmol/L)] differed accordingto A genotype.ThemeanIMTwas similar in the D I a I g ( e1 m 0n m
O l
0
m
. w es
o a
r f
.6 sd
a
cN T o Iv a o
2s 6
u o
@ ,k @
2
4C c
re e <
,
C oD . 3 e m i
M i
carotid,atherosclerosis, genetics
W
r ; t
9
y
p ce
in patientsconsideredto be at low risk in relationto traditionalrisk factors.In conclusion,our resultsdo not supporttheroleof the ACEgenotypeas a risk factorfor carotidatherosclerosis.
K
l
L
e
bloodflow
L O
L LOW [{UC K ( A1 E I f3el&dwLcon, AR D C R L V V
I U
I C
A G S @
1 M
S
O 0 OS T
B S 3 RN I E H M G %
O l
M M U
C
d
T ( r t i k f a a w p T a o s w e T p w h S p t g t A g s t ( w e h t b a s u a go 3 9 1 a 1 m s l w m ( w r c t t T b ( c X 5 H p s b b m a a s a s d w s t T v T v h s h t 2 T s h a n
( t
P
mE@Lcells, p< .OUOl)and plssm K+ (3.7MJ.4 Vs 4N.5 n!Eq/L, ,?< .orrl) levels Iban matched conlrol$ (MC). AD with hypcrlcnsivc Psronts(lll)) hml lower Ki than tbose wiOinormoicnsi.e psrcnts (Nl)) (90.2 f 5 Vs 93.4+5.5 mBq/L cells; p- .005). III the family groups (IW), all subjects hsd low Ki, but it wsr lower in the 111>($1.7*3.5 mEq/L CCII)thao in OICon%pring(01’) (86.4*6.3 mllq/L cell ). KLauUL ? I:W the I(KIsdult, IITnMI Mc, slro418 (-) correlatirm (Cor.) were obssrvcd belwccn Ki and IZORI DIN>(r= -.70. p= -.7) aml SISP (r_ -.65, p= -.65). I:or lbc 100 All Ki md SUP were (-) correlated & --.32 p- .tJ27). 01; with Ki < 25’b pact. had higher SRI’ (119 f 10 mmllg )Omn those will) Ki > 75’hpmt. (1 I I*7 mndlg; p <.01), rind hiaher aldosteronc levels (153*33 pghnl ) than those will] Ki > 25’k pmt. (104+16 pg/ml; p <.01). Amona the IQ strong (-) (k. were observed between Ki and f313P(r = -.48, p= .309) and S1ll>(r = -.38, P= : No significant Cor. were obxrval bctwccu J301).~ Ki sod other electrolytes. llowevcr in 11’1’,Ki wended 10WZNI(-) Cur. with Nai (r- ..16, p= ins.) and urinary K+ (F -.0S, p= n.s.). In All Ki also wended toward a (-) Cw. with Nai (-.05, p- n.s.) b ( w u
( . n t F 1 e 0 t t ( C w N ( . and r- .01, p= n,s,) and (-)wilh urinsry K+( r- -.04and r= -.12, p- n.s.). Finally, (he OR oflwwing low w 3.5 times gnxtcr it! Al) wi~h
MC
a
i d s l T a
RBC Ki, intermediate phenolype, genetic
o
C
f
HP than with N1’ (Chi-squrtre 7.60S4, p <,01). CONCLUSlON: wc dcmonztrskd Ihal estshlishcd hypertension is s.wocialed with low RISC Ki. OF with NP have lower Ki Ihan 0[7 of NP suggesting a role for hereditary factors in the control of RBC Ki.
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d w
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s v r w s t B e h t g T f d t w s t s p u n d s 1 a t W c t e d m e g t t w b t f g a i t O w t o p s T t Trp64Arg p v w s h t n o (o % p m y a c .s pn b r i ( 2 P s u d b p ( b h c n t t e ot T ( O s t c d w o b
h g
t
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I
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PC Ae
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The presence of low Ki was evnluatcd in 50 hyperlemives (44.5 ifl jrs) and in an age-matched nwmolcnsive aroup (n=50), in 100 adolcsccwt. ( i I yrs); am3 in [3 hypertcmive family groups (I4 hypcrkmsivc psrznw): 50.2*5 yrs; 37 offspriog:24 + IS yrs). Wood PII, Ki, IUIC Na. plasma and urine cdeclrolyles were measured in all suhjccts, Plasma aldoslerone and PRA were dclermitvxl in 15 adolcscmls (Al)). IwWIL’I”S: ~: Ilyperlensivcs (11’1’)had lower Ki (81.3+4 Vs Y3..Yi6
W
.
A SO A S NC O G O C I N I O W CL AM E G P NO Y ZE OI A W TR H T I AE C R JF . AE J R e J F u Hl C H i ar di hu B D o o eE cp pB i iac d o r ae c t a p A n hc T veg Fo a o i bn s h rR e uo r n egp d s i Vo s w c D au l a a ) r A c n e o (g i ni n n s ov eA rt e z d polymorphismhas been shown to be an ( J / h p M s u independentrisky factor for myecardizd infarction. F
massindex([email protected]#m2,andfastingsemrnlipid cawc@adonswcm:totaleboleatesol, 205rr@; L e h 4 rn hSignifrcsrttsib-sib r og 1 r H c cmrclsdon’s wereobserwdfornreandsepingsystokbloodprcssurs (r=O.63, p<0.0.01)aadrrreatr s b p
K
ClinicalGenetics 195A 1 O V POSTERS: H O U R L L
.
L O
L
K
A-
c h
g
a
i
bl
w
m t
r =
m
e
t s a s T f A g ( a 1 w O d t f ar w t t t t r g h b p s A
3
p i
g
t u
O T
. t
r
i u t r n
y r
:
1
J
1 N 9 4 PH
2
9
-
8
A
BLGDDFRESSURE HESITAB~OFBLGODFRES8UREAND A3mrcAN DE2ERM3NANR3 fNHYPERTEHs3wmYaLrFrDEMtc AWCmvIcy, CEGrim*, TAKotchen*, m@mrcANs.= PHanret*, HJaeob,JhfKotchm,RRomatLMe&alc of
WiscOrrs@ Milwaukee, WI. AflkatrArrre4iearu (AA)havca b i g Tlrepurpoaaofthis rcportisto a n d d( c ia C r Ofrnetabcdic, rezkal, and dedcribc evidmceforbsritabitity o i 4f A Cardiovasdardctemkm orcorrcfatea sibpairs(SSS18-55years),withesehsib havingbotbhyprtarsion m andSCrtU2t CbOtSStSfOl >200ttrgAU. Basedon24-bmrr ” padentbtood p p
m w
( As
i a s ev b oy d c sd te associated s d with o sACEJ/Dpolymorphism. t i rt s a au Ini this o study, as o z r 142rnrrdfsand86tnmH& K+ectkdy. Meaobodya$ f a r IMTwasdefinedasthemeanof IM’fmeasurements at 12
m h
m a w . =a s r in 0 r observed istribgsib-aibcodadeowas g u n for t 1
c
-
m er 2 a e awakediastolicbloodp p 0 butnotforawakc Systokbloodtrn=w . = 1 0 Signi6earrt sib-sibeomdationswereab?o obsefvcdlbr:bodysurfacc amaandbodySrrase iraiex;Skirrfdd dkkncssmmssuedateaveral renalbloodflOW sites;fkstingbloodghtwscandHDLchok@emi; (PAHCI earancc)bebre,atrdinsespenscto gradsdirttiisiorrs of 220rcPinct2hrir3e (-w; S1-arfittrrrtion rata(iaulirrckrancc)in “ mmmmnK@ Oftdvmtricutsr ~~w ~ diastoleard massandM Vsrrt2ieutar internaldianwendurisrg tmtybcthe duringsystolc.Thus,inAAj.sIcepiqbtoedpre=uras mostreliableblocdpresaura pbmotyps&wwaktingtwitabilityof hypcneasion. Haritabtsattcmtions ofrmalihnctiq ghrcoaeand fipidmctabob “m andheartsiznsaycOrltZibute totbehigh prcvsdemce ofhypcrtsesioe andhypsrtmsive CVDinM. (
W
O O
studieshave determinedwhethercwotid artery intima media thickness (MT) in aaymptomaticsubjects is
o r rm
P 0
A r
~
c
h
t
lr
ut o e -
sites of the carotidarteriesusing B-modeultrasound. ACEI/Dpolymorphism o kwas determined s in 355 healthy D r e men(54*7years)recruitedfrom adsurveyof rk 3 / e g t / a random m l d D sample of Southern Europe. The ACE genotype equilibrium[DD, r distribution l was in Hardy-Weinberg e s o 135(38%}ID, 150(42%);II, 70 (20%)].None ofa the e 7 ) ds cr t 0 kr n e . ai d 1 me4r v recognizedriskfactors[age,smokinghistory(21%were i current smokers), f l blood pressure i c c84+10 a s \137k16, 0 vbodymassindex(2fxt4kg/m), r s u diabetes(6%), eu t r r s s mmHg), 0 3 fasting plasma. glucose level5 (5.94*1.18 rmnrWL), 2 ) fasting plasma total cholesterol level (6.02i0.98 mmol/L),LDLcholesterollevel (3.85M195mrrroUL), triglyceride level (1.45ti.99 mmol/L)] differed accordingto A genotype.ThemeanIMTwas similar in the D I a I g ( e1 m 0n m
O l
0
m
. w es
o a
r f
.6 sd
a
cN T o Iv a o
2s 6
u o
@ ,k @
2
4C c
re e <
,
C oD . 3 e m i
M i
carotid,atherosclerosis, genetics
W
r ; t
9
y
p ce
in patientsconsideredto be at low risk in relationto traditionalrisk factors.In conclusion,our resultsdo not supporttheroleof the ACEgenotypeas a risk factorfor carotidatherosclerosis.
K
l
L
e
bloodflow
L O
L LOW [{UC K ( A1 E I f3el&dwLcon, AR D C R L V V
I U
I C
A G S @
1 M
S
O 0 OS T
B S 3 RN I E H M G %
O l
M M U
C
d
T ( r t i k f a a w p T a o s w e T p w h S p t g t A g s t ( w e h t b a s u a go 3 9 1 a 1 m s l w m ( w r c t t T b ( c X 5 H p s b b m a a s a s d w s t T v T v h s h t 2 T s h a n
( t
P
mE@Lcells, p< .OUOl)and plssm K+ (3.7MJ.4 Vs 4N.5 n!Eq/L, ,?< .orrl) levels Iban matched conlrol$ (MC). AD with hypcrlcnsivc Psronts(lll)) hml lower Ki than tbose wiOinormoicnsi.e psrcnts (Nl)) (90.2 f 5 Vs 93.4+5.5 mBq/L cells; p- .005). III the family groups (IW), all subjects hsd low Ki, but it wsr lower in the 111>($1.7*3.5 mEq/L CCII)thao in OICon%pring(01’) (86.4*6.3 mllq/L cell ). KLauUL ? I:W the I(KIsdult, IITnMI Mc, slro418 (-) correlatirm (Cor.) were obssrvcd belwccn Ki and IZORI DIN>(r= -.70. p= -.7) aml SISP (r_ -.65, p= -.65). I:or lbc 100 All Ki md SUP were (-) correlated & --.32 p- .tJ27). 01; with Ki < 25’b pact. had higher SRI’ (119 f 10 mmllg )Omn those will) Ki > 75’hpmt. (1 I I*7 mndlg; p <.01), rind hiaher aldosteronc levels (153*33 pghnl ) than those will] Ki > 25’k pmt. (104+16 pg/ml; p <.01). Amona the IQ strong (-) (k. were observed between Ki and f313P(r = -.48, p= .309) and S1ll>(r = -.38, P= : No significant Cor. were obxrval bctwccu J301).~ Ki sod other electrolytes. llowevcr in 11’1’,Ki wended 10WZNI(-) Cur. with Nai (r- ..16, p= ins.) and urinary K+ (F -.0S, p= n.s.). In All Ki also wended toward a (-) Cw. with Nai (-.05, p- n.s.) b ( w u
( . n t F 1 e 0 t t ( C w N ( . and r- .01, p= n,s,) and (-)wilh urinsry K+( r- -.04and r= -.12, p- n.s.). Finally, (he OR oflwwing low w 3.5 times gnxtcr it! Al) wi~h
MC
a
i d s l T a
RBC Ki, intermediate phenolype, genetic
o
C
f
HP than with N1’ (Chi-squrtre 7.60S4, p <,01). CONCLUSlON: wc dcmonztrskd Ihal estshlishcd hypertension is s.wocialed with low RISC Ki. OF with NP have lower Ki Ihan 0[7 of NP suggesting a role for hereditary factors in the control of RBC Ki.
M
d w
s
h
s
n
K
W
t n a
f G
t w t d E
6
m
t
r
b
s h b
t
c b
of
e
l
h
b p m
I
>
M
s v r w s t B e h t g T f d t w s t s p u n d s 1 a t W c t e d m e g t t w b t f g a i t O w t o p s T t Trp64Arg p v w s h t n o (o % p m y a c .s pn b r i ( 2 P s u d b p ( b h c n t t e ot T ( O s t c d w o b
h g
t
q
I
I r
i
PC Ae
M S
f s 7 gs o g
t
t
r
W ,
GT
I
The presence of low Ki was evnluatcd in 50 hyperlemives (44.5 ifl jrs) and in an age-matched nwmolcnsive aroup (n=50), in 100 adolcsccwt. ( i I yrs); am3 in [3 hypertcmive family groups (I4 hypcrkmsivc psrznw): 50.2*5 yrs; 37 offspriog:24 + IS yrs). Wood PII, Ki, IUIC Na. plasma and urine cdeclrolyles were measured in all suhjccts, Plasma aldoslerone and PRA were dclermitvxl in 15 adolcscmls (Al)). IwWIL’I”S: ~: Ilyperlensivcs (11’1’)had lower Ki (81.3+4 Vs Y3..Yi6
W
.
A SO A S NC O G O C I N I O W CL AM E G P NO Y ZE OI A W TR H T I AE C R JF . AE J R e J F u Hl C H i ar di hu B D o o eE cp pB i iac d o r ae c t a p A n hc T veg Fo a o i bn s h rR e uo r n egp d s i Vo s w c D au l a a ) r A c n e o (g i ni n n s ov eA rt e z d polymorphismhas been shown to be an ( J / h p M s u independentrisky factor for myecardizd infarction. F
massindex([email protected]#m2,andfastingsemrnlipid cawc@adonswcm:totaleboleatesol, 205rr@; L e h 4 rn hSignifrcsrttsib-sib r og 1 r H c cmrclsdon’s wereobserwdfornreandsepingsystokbloodprcssurs (r=O.63, p<0.0.01)aadrrreatr s b p
K
ClinicalGenetics 195A 1 O V POSTERS: H O U R L L
.
L O
L
K
A-
c h
g
a
i
bl
w
m t
r =
m
e
t s a s T f A g ( a 1 w O d t f ar w t t t t r g h b p s A
3
p i
g
t u
O T
. t
r
i u t r n
y r
: