The Effect of Apolipoprotein E Polymorphism on Hypertension in Korean Adults

B a c k g r o u n d : Apolipoprotein E has been one of the most thoroughly studied genetic polymorphisms, particularly for its effects on lipid profiles and coronary heart disease risk.

This study investigated the relationship between the apolipoprotein E polymorphism and essential hypertension in a Korean population.

M e t h o d s : The subjects (n=1,243) were participants in a population-based study in Incheon metropolitan City, Korea. The apolipoprotein E polymorphism was determined using a polymerase chain reaction method.

R e s u l t s : The frequencies of the genotypes did not differ significantly between the hypertensive groups (60.0% ȿ2 /ȿ2, 30.8% ȿ2 /ȿ3, 44.4% ȿ2 /ȿ4, 33.3% ȿ3 /ȿ3, 32.3% ȿ3 /ȿ4 , and 15.4% ȿ4 /ȿ4; p=0.498). After adjusting for other risk factors, genotypes were not associated with hypertension(OR 5.74, 95% CI 0.81-40.76, ȿ2 /ȿ2 vs. ȿ3 /ȿ3; OR 0.94, 95%

CI 0.60-1.47, ȿ2 /ȿ3 vs. ȿ3 /ȿ3; OR 1.21, 95% CI 0.30-4.89, ȿ2 /ȿ4 vs. ȿ3 /ȿ3; OR 0.79, 95%

CI 0.56-1.13, ȿ3 /ȿ4 vs. ȿ3 /ȿ3; OR 0.29, 95% CI 0.06-1.45, ȿ4 /ȿ4 vs. ȿ3 /ȿ3).

C o n c l u s i o n s: These findings suggest that the apolipoprotein E polymorphism is not associated with hypertension.

Key words : Apolipoprotein E, Polymorphism, Hypertension

고혈압과 apolipoprotein E의 다형성

㾲╖ἓ

, ₖ⁞䞮

, ⹫㌗䡚

, 㧚㩫㑮

Ṗ㻲㦮䞯㩚ⶎ╖䞯㤦 㡞⹿㦮䞯ὒ

, Ṗ㻲㦮䞯㩚ⶎ╖䞯㤦 ⌊ὒ

, 㩲㭒╖䞯ᾦ 㦮ὒ╖䞯 Ⱎ䀾䐋㯳㦮䞯ὒ

The Effect of Apolipoprotein E Polymorphism on Hypertension in Korean Adults

Dae-Kyung Choi

, Geum-Ha Kim

, Sang-Hyun Park

, Jeong-Soo Im

D e p a rtment of Preventive Medicine, Gachon Medical School

, Incheon, Korea;

D e p a rtment of Internal Medicine

, Gachon Medical School, Incheon, Korea;

D e p a rtment of Anesthesiology and Pain Medicine

, Cheju National University School of Medicine, Cheju, Kore a

୙ABSTRACT୙

J Agri Med & Community Health 2007;32(2):87~96

* ᾦ㔶㩖㧦: 㧚㩫㑮, 㧎㻲㔲 ⋾☯ῂ ῂ㤪1☯ 1 1 9 8, 㩚䢪: 0 3 2 - 4 6 0 - 3 8 3 3, 䕿㓺: 032-468-2154 E-mail: m d j s i m @ g a c h o n . a c . k r

昢 嵦

ἶ䡞㞫㦖 ␢㫎㭧, 㕂⁒ἓ㌟㯳, 㤎䡞㎇ 㕂⿖

㩚, 㔶㧻⼧, Ⱖ㽞䡞ὖ㰞䢮ὒ ṯ㦖 㕂䡞ὖ㰞䢮 㦮 㭒㣪 㥚䠮㣪㧎㧊┺[1]. 㤆Ⰲ⋮⧒㦮 ἶ䡞㞫 㥶⼧⮶㦖 ˈ 㫆㌂ ╏㔲 㑮㿫₆䡞㞫㧊 140 mmHg 㧊㌗㧊Ệ⋮ 㧊㢚₆䡞㞫㧊 90 mmHg 㧊㌗㧎 ἓ㤆 ⡦⓪ 㫆㌂ ╏㔲 䟃ἶ䡞㞫㩲⯒ ⽋ 㣿䞮ἶ 㧞⓪ ἓ㤆ˉ⯒ ₆㭖㦒⪲ 䞮㡖㦚 ➢ 3 0

㎎ 㧊㌗㦮 ㎇㧎㠦㍲ ⋾㧦⓪ 30.2%, 㡂㧦⓪ 2 5 . 6 %㠦 㧊⯎┺ἶ 䞲┺[ 2 ] .

㩚㼊 ἶ䡞㞫㦮 8 0 - 9 5 %⯒ 㹾㰖䞮ἶ 㧞⓪ ⽎ 䌲㎇ ἶ䡞㞫㦖 ⁎ 㤦㧎㦚 䢫㔺䞮Ợ 㞢 㑮 㠜 㦒⋮ 㰖⁞₢㰖 ⹳䡖㰚 㦮㕂♮⓪ ⳝ Ṗ㰖 㣪㧎 㦒⪲ 㥶㩚㩗 㣪㧎, 㔳㧊㔋ὖ, 䦷㡆, 㦢㭒, ゚Ⱒ, 㓺䔎⩞㓺, 㤊☯⿖㫇 ❇㦚 ✺ἶ 㧞┺. 䔏䧞 㥶㩚 㩗 㣪㧎㦖 㟧䂲㧊 ⳾⚦ ἶ䡞㞫㧊Ⳋ ⁎ 㧦⎖㦮 㟓 80% 㩫☚Ṗ ἶ䡞㞫㧊 ♮ἶ, 㟧䂲 㭧 䞲㴓 㧊 ἶ䡞㞫㧊Ⳋ ⁎ 㧦⎖㦮 4 0 - 5 0 %Ṗ ἶ䡞㞫㧊

♲┺⓪ Ṗ㫇㰧㩗㎇㦚 ⁎ ⁒Ệ⪲ 䞮ἶ 㧞⓪◆

[1], 䡚㨂₢㰖 ἶ䡞㞫㠦 ὖ㡂䞮⓪ 㥶㩚㧦 䢏㦖 䚲㰖㥶㩚㧦⯒ ⹲Ὴ䞮₆ 㥚䞲 䢮㧦-╖㫆ῆ 㡆 ῂ㠦㍲⓪ ἶ䡞㞫㦮 ⼧䌲㌳Ⰲ₆㩚 㭧 㭒⪲ ⩞

┢-㞞㰖㡺䎦㔶Ἒ(renin-angiotensin system, RAS), ᾦṦ㔶ἓἚ( c a t e c h o l a m i n e r g i c / a d r e n e r g i c function), 㔶㧻㌗䞒㦮 ⋮䔎⮾ 㺚⍦( s o d i u m epithelial channel), ㌆䢪㑮㏢ 㦮㫊㎇ 䢏㦖 ☛Ⱃ

㎇ 䡞 ὖ 㑮 㿫 ὒ 䡞 ὖ ゚ ╖ (nitric oxide dependent/independent vasodilation) ❇㦮 ₆㩚 㠦 ㏣䞮⓪ 㥶㩚㧦✺㦚 䤚⽊ 㥶㩚㧦⪲ ㌂㣿䞮 㡂 㢪┺[3]. 䞮㰖Ⱒ ⼧㤦㦚 ₆⹮㦒⪲ 䞲 㡆ῂ Ṗ 㞚┢ 㧒⹮ 㧎ῂ㰧┾㦚 ₆⹮㦒⪲ 䞲 㠊⟺

㡆ῂ㠦㍲☚ 㧊✺ 㥶㩚㧦㢖 ἶ䡞㞫ὒ㦮 ὖ⩾㎇

㦖 ⹳䡖㰖㰖 㞠㞮㦒Ⳇ, ┺⯎ Ⱒ㎇㰞䢮ὒ Ⱎ㺂 Ṗ㰖⪲ 㥶㩚㩗 㣪㧎ὒ 䢮ἓ 㣪㧎㦮 ㌗䢎㧧㣿 㠦 㦮䟊 ἶ䡞㞫㧊 ⹲㌳䞮⸖⪲ 㥶㩚㩗 㣪㧎㦚 ῂ㼊㩗㦒⪲ ⹳䧞₆Ṗ 㓓㰖 㞠⓪ 䡫䘎㧊┺[ 4 ] .

Apolipoprotein E(㧊䞮 A P O E )⓪ 2 9 9Ṳ㦮 㞚

⹎ ⏎ ㌆ 㦒 ⪲ ῂ㎇♲ ┺䡫㎇ ╏ ┾ ⺇ 㰞 (polymorphic glycoprotein)⪲㍲ 㰖㰞╖㌂ὒ㩫㠦

㭧㣪䞲 㡃䞶㦚 䞲┺. APOE⓪ 1 9⻞㱎 㡒㌟㼊 㦮 㧻㢚㠦 㥚䂮䞮⓪◆, 6Ṗ㰖 㥶㩚㧦䡫㧊 㧞┺.

㧊✺㦮 ㎎ Ṗ㰖㦮 㭒㣪 ╖Ⱃ㥶㩚㧦( a l l e l e ) ✺㦖 ȿ2, ȿ3 ⹥ ȿ4⪲ 䚲㔲♮ἶ, ⚦ Ṳ㦮 ╖Ⱃ㥶㩚㧦 Ṗ 䞲 㕣㦚 㧊⬾㠊 ṗṗ ☯䡫㩧䞿㼊(ȿ2 /ȿ2, ȿ3 / ȿ3, ȿ4 /ȿ4) ⡦⓪ 㧊䡫㩧䞿㼊(ȿ2 /ȿ3, ȿ2 /ȿ4, ȿ3 /ȿ 4) 䡫䌲⪲ ⹲䡚䞲┺[5]. 䡚㨂 㤆Ⰲ⋮⧒㠦㍲ 䦪 䞲 APOE 㥶㩚㧦䡫㦮 ⿚䙂⓪ 儒 2 /ȿ2 0.5%, ȿ2 /ȿ 3 9.5%, ȿ2 /ȿ4 0.8%, ȿ3 /ȿ3 72.9%, ȿ3 /ȿ4 15.3%, ȿ4 /ȿ4 0.9%⪲ 㞢⩺㪎 㧞┺[6]. APOE 㥶㩚㧦

⓪ 㞢㸪䞮㧊Ⲏ ⼧㦮 㥶㩚㩗 㥚䠮㧎㧦⪲ 㞢⩺

㪎 㧞㦒Ⳇ, ☯ⰻἓ䢪㯳, ὖ㌗☯ⰻ㰞䢮, ╖␢ 㥶 㩚⿚䡞ὖ⼧㯳(amyloid angiopathy) ❇㦮 㡂⩂

㕂㧻䡞ὖ㰞䢮㦮 ⹲㌳ ゞ☚Ṗ ⏨┺ἶ 㞢⩺㪎 㧞┺[7]. ⡦䞲 ╏␾, ⮮Ⱎ䏶㧊✲ ὖ㩞㡒, 䕢䋾 㓺⼧, 㩫㔶⿚㡊㯳, 㩫㔶⼧, ȼ 䌞⧒㎎⹎㞚 ❇ὒ 㦮 ὖ⩾㎇☚ 㩲₆♮ἶ 㧞┺[8-16]. 䔏䧞 㕂㧻 䡞ὖ㰞䢮㦮 ⹲㌳㠦 ὖ䟊㍲⓪ A P O EṖ ☛Ⱃ㩗 㧎 㥚䠮㣪㧎㦒⪲ 㧧㣿䞲┺⓪ Ṗ㍺ὒ 䆲⩞㓺䎢

⪺ὒ 㰖┾⺇㦮 㫆㩞㠦 ὖ㡂䞲┺⓪ ⚦ Ṗ㰖 Ṗ

㍺㧊 㫊㨂䞲┺. 㧊✺ Ṗ㍺㦖 ⿖Ỗ 㫆㰗 ㏢ἂ, 䡞ὖ㫆㡗㑶 ㏢ἂ, ἓ☯ⰻ⚦℮㦮 䁷㩫 ❇㦚 䐋 䞲 ὖ䁷ὒ 㡂⩂ 㧎ῂ㰧┾㦚 ╖㌗㦒⪲ 䞲 㡃䞯 㫆㌂⯒ 䐋䟊 㰖㰖⯒ ⹱ἶ 㧞┺. ╖′⳾㦮 㡃䞯 㫆㌂ ἆὒ㠦 㦮䞮Ⳋ ȿ3 /ȿ3 㥶㩚㧦⯒ ₆㭖㦒⪲

䞮㡖㦚 ➢, ȿ2 㥶㩚㧦⓪ 㽳䆲⩞㓺䎢⪺ 㑮䂮⯒

⌄㿮 ⹮Ⳋ, ȿ4 㥶㩚㧦⓪ ⏨㧎┺. ⁎Ⰲἶ, 㧊⩂

䞲 ἆὒ⓪ 㥶㩚㩗 ⺆ἓ, 㔳㧊, 㤊☯ 㔋ὖ㦮 㹾 㧊㠦☚ ⿞ῂ䞮ἶ 㡂⩂ ῃṖ㢖 㧎㫛㠦㍲ ὖ䁷

♲┺[5]. 㤆Ⰲ⋮⧒㠦㍲⓪ ȿ2 㥶㩚㧦㦮 㽳䆲⩞

㓺䎢⪺ ⹥ LDL 㑮䂮Ṗ ȿ3 ⹥ ȿ4 㥶㩚㧦㠦 ゚ 䞮㡂 㥶㦮䞮Ợ ⌄㦖 ộ㦒⪲ ⋮䌖⌂┺[6].

㧊⩝❅ APOE 㥶㩚㧦㢖 㕂㧻䡞ὖ㰞䢮ὒ㦮 ὖ⩾㎇㠦 ╖䟊 ῃ⌊㣎㠦㍲ Ⱔ㦖 㡆ῂṖ 㧊⬾

㠊㰖ἶ 㧞⓪◆, 㩫㧧 㤆Ⰲ⋮⧒ ῃ⹒㦮 1/4 㧊

㌗㧊 㞩ἶ 㧞⓪ ἶ䡞㞫ὒ APOE 㥶㩚㧦㦮 ὖ

⩾㎇㠦 ╖䞲 㡆ῂ⓪ 㞚㰗 㠜⓪ 㔺㩫㧊┺. 㧊⓪ ἶ䡞㞫 㧦㼊⪲ 㧎䞲 ㌂ⰳ㧊 ⁎Ⰲ Ⱔ㰖 㞠ἶ,

┺⯎ 㕂㧻䡞ὖ㰞䢮㻮⩒ 㫆㰗䞯㩗㧎 ⼖䢪⯒ ὖ

䁷䞶 㑮 㧞⓪ ⹿⻫㧊 㠜₆ ➢ⶎ㧒 ộ㧊┺. ➆

⧒㍲ ⽎ 㡆ῂ㠦㍲⓪ 㰖㡃㌂䣢 㧎ῂ⯒ ╖㌗㦒

⪲ ἶ䡞㞫 䢮㧦㠦㍲ APOE ┺䡫㎇㦮 ⿚䙂⯒

㞢㞚⽊ἶ, ἶ䡞㞫ὒ APOE ┺䡫㎇ ⿚䙂Ṗ 㡆 ὖ㎇㧊 㧞⓪Ṗ⯒ 㫆㌂䞮ἶ㧦 䞮㡖┺.

堆旇 愕 愯憛

APOE ❇ 㥶㩚㼊Ỗ㌂㠦 ☯㦮䞲 2 0㎎ 㧊㌗

㧎㻲ὧ㡃㔲 㔲⹒㦚 ╖㌗㦒⪲ 2 0 0 5⎚ 1 0㤪 1 7㧒

⿖䎆 1 1㤪 1 8㧒₢㰖 ㍺ⶎ㫆㌂ ⹥ ỊṫỖ㰚㦚 㔲䟟䞮㡖┺. 㡆ῂ╖㌗㧦㦮 ㍶㩫㦖 㧎㻲ὧ㡃㔲 ṗ ῂ㦮 ㎎╖ ῂ㎇゚㠦 ⁒Ệ䞮㡂 ゚⪖⺆⿚⻫

㠦 㦮䞲 ┺┾䂋䢪㿪㿲(proportional stratified sampling) ⹿⻫㦚 ㌂㣿䞮㡖┺. ㍺ⶎ㫆㌂⓪ ㌂ 㩚㠦 㡆ῂ㦮 䀾㰖㢖 㫆㌂⹿⻫㠦 ╖䞮㡂 ᾦ㥷 㦚 ⹱㦖 㫆㌂㣪㤦✺㧊 㔲⹒✺ὒ Ⳋ㩧㠦 㦮䞮 㡂 㫆㌂䞮⓪ ⹿⻫㦒⪲ 㔺㔲䞮㡖┺. ㍺ⶎ㰖㦮 ῂ㎇㦖 ㎇, 㡆⪏, 䞯⩻, ㌂䣢ἓ㩲㩗 䔏㎇ ❇ 㧎 ῂ䞯㩗㧎 ⼖㑮㢖, 䦷㡆㌗䌲, 㦢㭒㌗䌲, 㧒㌗㌳

䢲 㔶㼊䢲☯㩫☚ ❇ ㌳䢲㔋ὖ ⼖㑮, ⁎Ⰲἶ 㰞

⼧⩻㠦 ╖䞲 㫆㌂䟃⳿㦒⪲ ῂ㎇♮㠞┺.

ỊṫỖ㰚㦖 㔶㧻, 㼊㭧, 䡞㞫, 㔳㩚䡞╏, 㽳䆲

⩞㓺䎢⪺ 䁷㩫 ⹥ APOE ❇㠦 ╖䞲 㥶㩚㼊Ỗ

㌂⪲ ῂ㎇♮㠞㦒Ⳇ, 㥶㩚㼊Ỗ㌂㠦 ╖䟊㍲⓪ Ṗ 㻲㦮╖㭧㞯₎⼧㤦 㧚㌗㔲䠮㥺Ⰲ㥚㤦䣢㦮 㔏㧎 㦚 ⹱㞮┺. 㔶㧻ὒ 㼊㭧㦮 䁷㩫㦖 ╖㌗㧦Ṗ Ṗ

⼒㤊 㢍㹾Ⱂ㦚 䞮ἶ, 㔶⹲㦚 ⻭㦖 ㌗䌲㠦㍲ 䁷 㩫䞮㡖㦒Ⳇ, 㔶㧻㦖 cm ┾㥚⪲, 㼊㭧㦖 kg ┾ 㥚⪲ 䁷㩫䞮㡖┺. 㧊⪲⿖䎆 㼊㰞⨟㰖㑮( k g / m

)

⯒ ῂ䞮㡖┺. 䡞㞫㦖 㾲㏢ 5⿚ ☯㞞㦮 㞞㩫₆

⯒ Ṭ☚⪳ 䞮₆ 㥚䟊 Ⲓ㩖 ㍺ⶎ㫆㌂⯒ 㔺㔲䞲 䤚㠦 䡞㞫㦚 䁷㩫䞮㡖┺. 䡞㞫 䁷㩫㦖 䤞⩾⹱

㦖 㫆㌂㣪㤦㧊 㑮㦖䡞㞫Ἒ⯒ 㧊㣿䞮㡂 2䣢 䁷 㩫䞮㡖ἶ, ⁎ 䘟‶Ṩ㦚 ⿚㍳㠦 㧊㣿䞮㡖┺. 䡞 㞫㦖 㞟㦖 㧦㎎⪲ 㕂㧻ὒ ṯ㦖 ⏨㧊㦮 㤆䁷

㌗⹫㠦㍲ 䁷㩫䞮㡖㦒Ⳇ, 㑮㿫₆䡞㞫㦖

Korotkoff phase ช, 㧊㢚₆䡞㞫㦖 K o r o t k o f f phase ญ/ฎ⯒ ₆㭖㦒⪲ 䞮㡖┺. 䡞㞫 ⿚⮮⓪ 2 0 0 3⎚㠦 Ṳ㩫♲ 㩲7㹾 ἶ䡞㞫 㡞⹿, ⹲ἂ, 䘟 Ṗ ⹥ 䂮⬢㠦 ὖ䞲 䞿☯㥚㤦䣢㦮 ⽊ἶ㍲( J N C -

ฐ)㦮 ₆㭖㠦 ➆⧒ 㑮㿫₆䡞㞫㧊 140 mmHg 㧊㌗㧊Ệ⋮ 㧊㢚₆䡞㞫㧊 90 mmHg 㧊㌗㧎 ἓ㤆, 㯟 㩲1₆ ἶ䡞㞫ὒ 㩲2₆ ἶ䡞㞫㠦 䟊╏

䞮⓪ ἓ㤆⯒ ἶ䡞㞫㦒⪲ 㩫㦮䞮㡖┺[ 1 7 ] . 䡞㞷Ỗ㌂⯒ 㥚䞲 䡞㞷㦮 㺚䀾⓪ 㩚⋶ 㩖⎗

㔳㌂ 㧊䤚 1 2㔲Ṛ 㧊㌗㦮 Ὃ⽋㌗䌲⯒ 㥶㰖䞮

☚⪳ 䞲 䤚 ┺㦢⋶ 㡺㩚㠦 㔲䟟䞮㡖┺. 䡞㼃 㰖㰞, 䡞╏ὒ APOE 䁷㩫㦚 㥚䟊 䡞㞷㦚 ⽊㫊 㩲Ṗ 㻾Ṗ♮㰖 㞠㦖 㰚Ὃ䓲ぢ㠦 㺚䀾䞮㡖㦒Ⳇ, 㺚䀾 㰗䤚⿖䎆 Ỗ㌂㔺㠦㍲ 㤦㕂⿚Ⰲ䞮₆ 㩚₢

㰖 㠒㦢㠦 ⽊ὖ䞲 㺚⪲ 㑮㏷䞮㡖┺. Ỗ㌂㔺㠦

☚㹿䞲 䡞㞷㦖 4ଇ㠦㍲ 3000 rpm㦒⪲ 1 0⿚ ☯ 㞞 㤦㕂⿚Ⰲ䞲 䤚㠦 Ỗ㌂㔺 Ỗ㌂⯒ 㔺㔲䞮㡖

┺. 䡞㼃 㰖㰞(㽳䆲⩞㓺䎢⪺, 㭧㎇㰖㰞, ἶ⹖☚

㰖┾⺇ 䆲⩞㓺䎢⪺)㦖 AU5400 㧦☯ ⿚㍳₆ (Olympus, Japan)⯒ 㧊㣿䞲 䚲㭖䢪♲ 䣾㏢⻫㦒

⪲ 䁷㩫䞮㡖ἶ, 㩖⹖☚㰖┾⺇ 䆲⩞㓺䎢⪺㦖 Friedwald 㔳㦚 㧊㣿䞮㡂 Ἒ㌆, 䁷㩫䞮㡖┺. 䡞

╏㦖 hexokinase-ultraviolet 䁷㩫⻫㠦 㦮䟊 Ascensia GLUCODISC(BAYER)⯒ 㧊㣿䞮㡂 䁷㩫䞮㡖┺. APOE ┺䡫㎇ Ỗ㌂⓪ Ⱖ㽞䡞㞷㦮

⺇䡞ῂ㠦㍲ 㿪㿲䞲 D N A⯒ 㭧䞿䣾㏢ 㡆㐚⹮㦧 (polymerase chain reaction; PCR)⻫㦒⪲ 㯳䙃 䞮㡖┺ . APOE㦮 㥶㩚㧦䡫㦖 Hixonὒ V e r n i e r [ 7 ] Ṗ ㍲㑶䞲 ₆㭖㦚 ⼖䡫䞮㡂 ȿ2 (ȿ2 /ȿ2 㢖 ȿ2 /ȿ3), ȿ3 (ȿ3 /ȿ3), ȿ4 (ȿ3 /ȿ4㢖 ȿ4 /ȿ4 )㢖 ṯ㧊 3Ṳ㦮 ⁎⭏㦒⪲ ⿚⮮䞮㡖┺. PCR㠦 ㌂㣿♲ 㔲

⹲㼊 1㦖 5ː -ACA GAATTCGCCCCGGCC T G G T A C A C - 3 ː 㧊ἶ 㔲⹲㼊 2⓪ 5ː - T A A G C T T G G C A C G G C T G T C C A A G G A - 3 㡖┺.

PCR 䢒䞿ⶒ㦖 㽳 㣿㩗 10 ື㦒⪲ 0.25 mM㦮 dNTP, 1.5mM 㡒䢪䃒㓮( M g C l 2), 0.75U 㥶㩚㧦 㭧䞿䣾㏢(Solgent, Seoul, Korea), 50 ng genomic DNA, 0,25 uM㦮 㔲⹲㼊 1ὒ 2⪲ ῂ㎇䞮㡖┺.

㥶㩚㧦㯳䙃₆ (PTC-200; MJ Research, Inc, Watertown, MA, U.S.A.)⯒ 㧊㣿䞮㡂 9 4ଇ㠦㍲

5⿚Ṛ D N A⯒ ⼖㎇㔲䋾 䤚, 94ଇ㠦㍲ 3 0㽞Ṛ

⼖㎇, 65ଇ㠦㍲ 4 0㽞Ṛ ἆ䞿, 72ଇ㠦㍲ 9 0㽞Ṛ 䢫㧻 㔲䋺⓪ ὒ㩫㦚 4 0䣢 ⹮⽋䞮ἶ Ⱎ㰖Ⱏ㦒

⪲ 7 2ଇ㠦㍲ 5⿚Ṛ 䢫㧻⹮㦧䞮㡂 P C R㦚 㔲䟟

䞮㡖┺. 㯳䙃㌆ⶒ㦚 㩲䞲䣾㏢㧎 HhaI (TaKaRa Co. Ltd., Kyoto, Japan) 5U⪲ ⹮㦧 㔲䋾 䤚, 10% polyacrylamide gel㠦 㩚₆㡗☯㦚 䞮㡂 ethidium bromide⪲ 㡒㌟䞲 䤚 㧦㣎㍶䞮 㠦㍲ APOE 㥶㩚㧦䡫㦚 ἆ㩫䞮㡖┺.

㧦⬢⿚㍳㦖 SPSS 11.0(Chicago, U.S.A.)㦚 㧊 㣿䞮㡂 䐋Ἒ⿚㍳㦚 㔺㔲䞮㡖┺. ₆㑶䐋Ἒ⪲⓪ 㔺㑮㢖 ⺇⿚㥾, 䘟‶ὒ 䚲㭖䘎㹾⯒ 㧊㣿䞮㡂 㡆ῂ╖㌗㧦㦮 䔏㎇⼚ ⿚䙂⯒ 㩫Ⰲ䞮㡖┺.

APOE ╖Ⱃ㥶㩚㧦㠦 ➆⯎ ἶ䡞㞫㦮 㥶⼧⮶㦚

㌆㿲䞮㡖ἶ, APOE㢖 ἶ䡞㞫ὒ㦮 ὖ⩾㎇㦖 ┺ 㭧 ⪲㰖㓺䕇 䣢‖⿚㍳㦚 㧊㣿䞮㡂 ᾦ㹾゚㢖 95% 㔶⬆ῂṚ㦚 㩲㔲䞮㡖┺. ᾦ㹾゚㢖 9 5 % 㔶⬆ῂṚ㦖 㡆⪏ὒ ㎇⼚Ⱒ㦚 ᾦ㩫䞲 ἓ㤆㢖 㡆⪏, ㎇⼚, 㼊㰞⨟㰖㑮, 㽳䆲⩞㓺䎢⪺, 䡞╏, 䦷㡆㡂⿖㢖 㦢㭒㡂⿖ ❇㧊 䢒⧖⼖㑮⯒ 䐋㩲䞲 ἓ㤆⪲ 㩲㔲䞮㡂 ὖ⩾㎇㦚 䕢㞛䞮㡖┺.

冶 刂

1. 櫶割堆旇沖汞 沂愞洇 瞿昷

㡆ῂ╖㌗㧦⓪ ⋾㧦 2 8 1ⳛ( 2 2 . 6ୁ), 㡂㧦 9 6 2ⳛ ( 7 7 . 4ୁ)㦒⪲ 㽳 1 , 2 4 3ⳛ㧊㠞┺. 䘟‶ 㡆⪏㦖 51.2(· 14.5)㎎㧊㠞ἶ, 䘟‶ 㼊㰞⨟㰖㑮⓪ 24.3(· 5.9) kg/m

㧊㠞┺. 㽳䆲⩞㓺䎢⪺㦖 1 9 2 . 7 (· 34.9) mg/ູ, Ὃ⽋㔲 䡞╏㦖 9 8 . 2 (·

25.3) mg/ູ㧊㠞┺. 㩚㼊 䘟‶ 㑮㿫₆䡞㞫ὒ 㧊㢚₆䡞㞫㦖 1 2 7 . 2 (· 17.5) mmHg, 79.7(·1 0 . 5 ) m m H g㧊㠞ἶ, ⋾㧦⓪ 1 3 2 . 9 (· 16.8) mmHg, 82.2(· 9.8) mmHg, 㡂㧦⓪ 125.5(· 17.4) mmHg, 78.9(· 10.6) mmHg㧊㠞┺. 㩚㼊 䦷㡆 㥾ὒ 㦢㭒㥾, ⁎Ⰲἶ 㤊☯㔺㻲㥾㦖 1 7 . 8 % , 37.7%, 47.4%㧊㠞ἶ, ⋾㧦⓪ 62.5%, 64.9%, 48.8%, 㡂㧦⓪ 4.8%, 29.2%, 47.0%㧊㠞┺.

䞲䘎 APOE ╖Ⱃ㥶㩚㧦㦮 ⿚䙂⓪ ȿ3 /ȿ3Ṗ 6 8 . 7 %⪲ Ṗ㧻 Ⱔ㞮ἶ, ȿ3 /ȿ4Ṗ 18.7%, ȿ2 /ȿ3Ṗ 1 0 . 5 %⯒ 㹾㰖䞮㡖┺. ȿ2 /ȿ2㢖 ȿ2 /ȿ4, ⁎Ⰲἶ ȿ 4 /ȿ4⓪ 1 %⯒ ⍮㰖 㞠㞮┺(Table 1).

2. APOE 堆廃氦洊沖櫖 娶幾 処笎橛 氦懗幦

APOE ╖Ⱃ㥶㩚㧦⼚⪲ ἶ䡞㞫 㥶⼧⮶㦚 㞢 㞚⽎ ἆὒ, ȿ2 /ȿ2 60.0%, ȿ2 /ȿ3 30.8%, ȿ2 /ȿ4 44.4%, ȿ3 /ȿ3 33.3%, ȿ3 /ȿ4 32.3%, ȿ4 /ȿ4 15.4%

㧊㠞┺. APOE ╖Ⱃ㥶㩚㧦⼚ ἶ䡞㞫 㥶⼧㥾㦖 䐋 Ἒ 㩗 㦒 ⪲ 㥶 㦮 䞲 㹾 㧊 Ṗ 㠜 㠞 ┺ (p>0.05)(Table 2).

3. APOE歆 処笎橛刂汞 分崮昷

APOE ╖Ⱃ㥶㩚㧦㠦 ➆⯎ ἶ䡞㞫 㥶⼧⮶ 㥚 䠮☚⯒ 㞢㞚⽊₆ 㥚䞲 ⪲㰖㓺䕇 䣢‖⿚㍳ ἆ ὒ A P O E㢖 ἶ䡞㞫㦖 䐋Ἒ㩗㦒⪲ 㥶㦮䞲 ὖ

⩾㧊 㠜㠞┺(p>0.05). 㡆⪏, ㎇, 㽳䆲⩞㓺䎢⪺, Ὃ⽋ 䡞╏, 㼊㰞⨟㰖㑮, 䦷㡆 㡂⿖㢖 㦢㭒 㡂⿖

❇㦮 䢒⧖⼖㑮⯒ 䐋㩲䞲 ㌗䌲㠦㍲ ἶ䡞㞫 㥶

⼧⮶㦮 ᾦ㹾゚⓪ ȿ3 /ȿ3⯒ ₆㭖㦒⪲ 䞮㡂 ȿ2 /ȿ2 5.737(95% CI=0.807-40.761), ȿ2 /ȿ3 0.936(95%

CI=0.595-1.472), ȿ2 /ȿ4 1.205(95% CI=0.297- 4.894), ȿ3 /ȿ4 0.794(95% CI=0.559-1.127), ȿ4 /ȿ4 0.285(95% CI=0.056-1.451)㧊㠞┺(Table 3).

処 然

␢㫎㭧, 㕂⁒ἓ㌟㯳, 㤎䡞㎇ 㕂⿖㩚, 㔶㧻⼧, Ⱖ㽞䡞ὖ㰞䢮 ❇ὒ ṯ㦖 㕂䡞ὖἚ 㰞䢮㦮 㥚 䠮㣪㧎 㭧 ⼖ἓ㧊 Ṗ⓻䞮Ⳇ, 㰞⼧ ⹲㌳㠦 Ṗ㧻 Ⱔ㦖 ⿖⿚㦚 㹾㰖䞮⓪ ộ㧊 ἶ䡞㞫㧊┺. 㾲⁒

㡆ῂἆὒ㠦 㦮䞮Ⳋ 㤆Ⰲ⋮⧒㠦㍲ ἶ䡞㞫㧊 ␢ 䡞ὖ㰞䢮ὒ 䠞䡞㎇ 㕂㧻 㰞䢮 ⹲㌳㠦 ₆㡂䞮

⓪ 㰖㡃㌂䣢 ₆㡂㥚䠮☚⓪ ṗṗ 3 5 %㢖 2 1 %⧒

ἶ 䞲┺[18]. 㧊⓪ 㧎ῂ㰧┾ 㩚㼊Ṗ 䡞㞫㠦 ╖ 䞲 㩗㩞䞲 䂮⬢㢖 ὖⰂ⪲ 㩫㌗䡞㞫㦚 㥶㰖䞶 㑮 㧞┺Ⳋ ␢䡞ὖ㰞䢮ὒ 䠞䡞㎇ 㕂㧻 㰞䢮㦚 ṗṗ 3 5 %㢖 21% 㡞⹿䞶 㑮 㧞㦢㦚 㦮⹎䞲┺.

➆⧒㍲ 㕂䡞ὖἚ 㰞䢮㦒⪲ 㧎䞲 㰞⼧⿖╊㦚 㭚㧊₆ 㥚䟊㍲⓪ ἶ䡞㞫㦮 ⹲㌳㦚 㡞⹿䞮₆ 㥚䞲 ⏎⩻㦚 䞮⓪ ộ㧊 ⰺ㤆 㭧㣪䞮┺.

ἶ䡞㞫㦮 㥚䠮㣪㧎㦖 ⣲⪍䞮Ợ ⹳䡖㰖㰖 㞠

㞮㦒⋮, ㎇, 㡆⪏, 㥶㩚㩗 㣪㧎, ゚Ⱒ, 㔳㡒 ㎃

䀾, 㦢㭒, 㔶㼊䢲☯⨟, 㔳㔋ὖ ❇㧊 㡂⩂ 㡃䞯

㩗 㡆ῂ✺㦚 䐋䟊 㞢⩺㪎 㧞┺. 䔏䧞 ἶ䡞㞫㦮

㥶㩚㥾 䢏㦖 䡞㞫⼖䢪㦮 㥶㩚㩗 ₆㡂☚⓪ 3 0 - 5 0 %⪲ 䘟Ṗ♮ἶ 㧞㠊 䢮ἓ㩗 㣪㧎 㣎㠦 㥶㩚 㩗 㣪㧎㧊 㹾㰖䞮⓪ ゚㭧㧊 ⏨㦢㦚 㞢 㑮 㧞

┺[19]. 䡚㨂₢㰖 ἶ䡞㞫ὒ 㥶㩚㩗 㣪㧎ὒ㦮 ὖ⩾㎇ 㡆ῂ⓪ 㭒⪲ ⩞┢-㞞㰖㡺䎦㔶Ἒ㠦 䟊

╏ 䞮 ⓪ Angiotensin-ช converting enzyme(ACE), Angiotensinogen(AGT), Angiotensin ซ type1 receptor(AT1R), Cytochrome p450 subfamily 11(CYP11B2) ❇㦮 㥶㩚㧦✺㦮 ┾㧒㡒₆┺䡫(Single nucleotide

polymorphism, SNP)㠦 ╖䟊㍲ Ⱔ㦖 㡆ῂ✺㧊

⽊ἶ♮ἶ 㧞⓪◆[3,20-30], ┺⯎ Ⱒ㎇㰞䢮ὒ Ⱎ 㺂Ṗ㰖⪲ 㥶㩚㩗 㣪㧎ὒ 䢮ἓ 㣪㧎㦮 ㌗䢎㧧 㣿㠦 㦮䟊 ἶ䡞㞫㧊 ⹲㌳䞮⸖⪲ 㥶㩚㩗 㣪㧎 㦚 ῂ㼊㩗㦒⪲ ⹳䧞₆Ṗ 㓓㰖 㞠⓪ 䡫䘎㧊┺

[4].

⽎ 㡆ῂ㠦㍲⓪ 㰖㡃㌂䣢 㧎ῂ⯒ ╖㌗㦒⪲

ἶ䡞㞫 䢮㧦㠦㍲ APOE ┺䡫㎇㦮 ⿚䙂⯒ 㞢 㞚⽊ἶ, ἶ䡞㞫ὒ APOE ┺䡫㎇ ⿚䙂Ṗ 㡆ὖ

㎇㧊 㧞⓪Ṗ⯒ 㫆㌂䞮ἶ㧦 䞮㡖┺. 㡆ῂ ἆὒ, Table 1. Characteristics of the subjects

V a r i a b l e s M a l e ( N = 2 8 1 ) F e m a l e ( N = 9 6 2 ) T o t a l ( N = 1 , 2 4 3 ) Age (yrs) 5 4 . 4· 1 5 . 0 5 0 . 3· 1 4 . 2 5 1 . 2· 1 4 . 5 Body mass index (kg/m

) 2 4 . 4· 3 . 2 2 4 . 0· 6 . 5 2 4 . 3· 5 . 9 Total cholesterol (mg/ູ) 1 9 1 . 4· 3 4 . 2 1 9 3 . 0· 3 5 . 1 1 9 2 . 7· 3 4 . 9 Triglyceride (mg/ູ) 1 5 5 . 8· 1 1 5 . 3 1 1 0 . 2· 6 9 . 7 1 2 0 . 5· 8 4 . 3 HDL-cholesterol (mg/ູ) 4 5 . 2· 1 2 . 8 5 1 . 6· 1 3 . 0 0 . 1· 1 3 . 2 Fasting blood sugar(mg/ູ) 1 0 2 . 5· 2 6 . 7 9 7 . 0· 2 4 . 7 9 8 . 2· 3 4 . 9 Systolic blood pressure (mmHg) 1 3 2 . 9· 1 6 . 8 1 2 5 . 5· 1 7 . 4 1 2 7 . 2· 1 7 . 5 Diastolic blood pressure (mmHg) 8 2 . 2· 9 . 8 7 8 . 9· 1 0 . 6 7 9 . 7· 1 0 . 5

Smoking (%) 6 2 . 5 4 . 8 1 7 . 8

Alcohol drinking (%) 6 4 . 9 2 9 . 2 3 7 . 7

Exercise (%) 4 8 . 8 4 7 . 0 4 7 . 4

APOE (%)

ȿ2 /ȿ2 0 . 0 0 . 5 0 . 4

ȿ2 /ȿ3 7 . 8 1 1 . 2 1 0 . 5

ȿ2 /ȿ4 0 . 7 0 . 7 0 . 7

ȿ3 /ȿ3 6 9 . 0 6 8 . 6 6 8 . 7

ȿ3 /ȿ4 2 1 . 7 1 7 . 8 1 8 . 7

ȿ4 /ȿ4 0 . 7 1 . 1 1.0

Table 2. Prevalence of hypertension by the allele of apolipoprotein E

A l l e l e N o r m a l ( % ) P r e h y p e r t e n s i o n ( % ) H y p e r t e n s i o n ( % ) p-value

ȿ2 /ȿ2 0 . 0 4 0 . 0 6 0 . 0 0 . 4 9 8

ȿ2 /ȿ3 2 5 . 4 4 3 . 8 3 0 . 8

ȿ2 /ȿ4 1 1 . 1 4 4 . 5 4 4 . 4

ȿ3 /ȿ3 2 6 . 9 3 9 . 8 3 3 . 3

ȿ3 /ȿ4 2 4 . 6 4 3 . 1 3 2 . 3

ȿ4 /ȿ4 3 8 . 5 4 9 . 1 15.4

ȿ2 /ȿ2㦮 ἶ䡞㞫 㥶⼧⮶㦖 60.0%, ȿ2 /ȿ3⓪ 30.8%, ȿ2 /ȿ4⓪ 44.4%, ȿ3 /ȿ3⓪ 33.3%, ȿ3 /ȿ4⓪ 32.3%, ȿ4 /ȿ4⓪ 1 5 . 4 %㧊㠞㦒Ⳇ, ╖Ⱃ㥶㩚㧦⼚

ἶ䡞㞫 㥶⼧⮶㦖 䐋Ἒ㩗㦒⪲ 㥶㦮䞲 㹾㧊Ṗ 㠜㠞┺. ⡦䞲 ȿ3 /ȿ3⯒ ₆㭖㦒⪲ 䞮㡂 ⪲㰖㓺䕇 䣢‖⿚㍳㦚 䞲 ἆὒ ἶ䡞㞫 㥶⼧⮶㦮 ᾦ㹾゚

⓪ ȿ2 /ȿ2Ṗ 5.737, ȿ2 /ȿ3Ṗ 0.936, ȿ2 /ȿ4Ṗ 1 . 2 0 5 , ȿ3 /ȿ4Ṗ 0.794, ⁎Ⰲἶ ȿ4 /ȿ4Ṗ 0 . 2 8 5㧊㠞㦒Ⳇ, A P O E㢖 ἶ䡞㞫㦖 䐋Ἒ㩗㦒⪲ 㥶㦮䞲 ὖ⩾㧊 㠜㠞┺.

⽎ 㡆ῂ㦮 䚲䡚䡫㦖 䢮㧦-╖㫆ῆ 㯟, ἶ䡞㞫 㥶ⶊ㧊┺. 㧒⹮㩗㦒⪲ 䚲䡚䡫㦚 㠊⠑Ợ 㩫㦮䞮

⓪⌦⓪ ⰺ㤆 㭧㣪䞲 ὖ㩦㧊Ⳇ, ⿚㍳⹿⻫ὒ ἆ ὒ☚ 䚲䡚䡫㠦 ➆⧒ ╂⧒㰞 㑮 㧞┺. 㯟, 䡞㞫 㦮 㧚Ἒ䂮 㑮㭖㠦 ➆⧒ ⿚⮮⻪㭒Ṗ ⹪≢Ợ ♮ ἶ 㧊ộ㦖 㥶㩚㧦㦮 ὖ⩾㎇㠦 㡗䟻㦚 㭒₆ ➢ ⶎ㠦 䡞㞫㑮㭖㦚 㡆㏣䡫㦒⪲ ⿚㍳䞮⓪ 㟧㩗䡫 㰞⿚㍳㧊 䞚㣪䞶 㑮☚ 㧞┺[20]. ⽎ 㡆ῂ㠦㍲

㥶㩚㧦㦮 ㍶㩫㦖 ἶ䡞㞫 㰚┾㠦 㧞㠊 㡆㐚 䢏 㦖 㡆ὖ㎇㧊 䘟Ṗ♲ 㥶㩚㧦 㯟 䡞㞫⼖䢪㠦 ╖ 䟊 ㎎䙂㌳Ⰲ㩗 ₆㩚㧊 㧮 㞢⩺㰚 㥶㩚㧦⯒ ╖

㌗㦒⪲ 䞮㡖┺. 䤚⽊㥶㩚㧦㌗㠦 ⿚䙂䞮⓪ 㡂⩂

㫛⮮㦮 ╖Ⱃ㧎㧦 ┺䡫㎇㠦 ὖ䞲 㡆ῂ ἆὒ㠦

➆⯊Ⳋ ╖Ⱃ㧎㧦㦮 ゞ☚ ⹥ 㰞⼧ὖ⩾ 㥶㩚㧦 㦮 ὖ⩾㎇ 㡆ῂἆὒṖ 㥶㌂䞲 ἓ㤆☚ Ⱔ㦒⋮

㥶㩚㧦㠦 ➆⧒ ┺⯎ ⹒㫇 㰧┾㠦㍲⓪ ゚ᾦ㩗

⏨㦖 ゞ☚⪲ ⽊ἶ♮㠞㦢㠦☚ ⿞ῂ䞮ἶ 䞲ῃ㧎 㠦㍲⓪ ⰺ㤆 ⌄㦖 ゞ☚⪲ ⹲ἂ♮㠊 㰞⼧ὖ⩾

┺䡫㎇㦒⪲㍲㦮 㦮㦮Ṗ 㠜Ệ⋮ 㧊㢖⓪ ⹮╖⪲

┺⯎ ⹒㫇㠦㍲⓪ ⽊ἶ♮㰖 㞠㞮▮ 㥶㩚㧦 ⼖ 㧊Ṗ 䞲ῃ㧎㠦㍲ ⏨㦖 ゞ☚⪲ ὖ㺆♮⓪ ἓ㤆 Ṗ 㧞㠊 㥶㩚㧦 ┺䡫㎇㦖 ⹒㫇Ṛ ゞ☚ ⹥ 㧚

㌗㩗 㦮㦮㠦 ➆⧒ 㹾㧊Ṗ 㧞┺. 㡞⯒ ✺㠊 㧒

⽎㧎ὒ 㭧ῃ㧎㠦㍲ ACE I/D㦮 D ╖Ⱃ㥶㩚㧦

⓪ ἶ䡞㞫ὒ ὖ⩾㎇㧊 㧞⓪ ⹮Ⳋ 㓺䗮㧎㦚 ╖

㌗㦒⪲ 䞲 㡆ῂ ❇ Ⱔ㦖 㡆ῂ㠦㍲⓪ ⡦䞲 ὖ

⩾㎇㧊 㠜⓪ ộ㦒⪲ ⋮䌖⌂┺[21,22]. ⁎⩂⋮

㾲⁒ Porto[23] ❇㧊 㼃㏢⎚㦚 ╖㌗㦒⪲ 㔺㔲 䞲 䢮㧦-╖㫆ῆ 㡆ῂ㠦 㦮䞮Ⳋ A C E / I D㢖 A G T㦮 㥶㩚㩗 ⼖㧊㢖 ㌗䢎㧧㣿㦖 ἶ䡞㞫 ⹲

㌳㠦 ⰺ㤆 㭧㣪䞲 㤦㧎㦒⪲ 㧧㣿䞲┺ἶ ⽊ἶ

♲ ⹪ 㧞┺. ⡦ ┺⯎ 㡞⪲ 㧒⽎㧎ὒ 㭧ῃ㧎㠦

㍲ Alpha adducin(ADD1) 㥶㩚㧦⌊ 㠧㏦( e x o n ) 1 0⻞㦮 G 4 6 0 WṖ ἶ䡞㞫ὒ ὖ⩾㎇㧊 㧞⓪ ộ 㦒⪲ ⽊ἶ♲ ⹮Ⳋ[29], 㤆Ⰲ⋮⧒ 㧒⹮㧎ῂ㰧┾

㦚 ╖㌗㦒⪲ 㔺㔲䞲 䢮㧦-╖㫆ῆ 㡆ῂ㠦㍲⓪ ἶ䡞㞫ὒ ὖ⩾㎇㧊 㠜⓪ ộ㦒⪲ ⽊ἶ♲ ⹪ 㧞

┺[ 3 0 ] .

㌂⧢㧊 䢮ἓ㣪㧎㠦 㡗䟻㦚 ⹱⓪ 㩫☚⓪ 㥶 㩚㩗㧎 ⌊㎇㧊⋮ Ṧ㑮㎇㠦 ➆⧒ ╂⧒㰚┺. ὖ

㌗☯ⰻ㰞䢮 ⹲㌳㦮 ἓ㤆 5 0㎎ 㧊䞮㦮 㩠㦖 㡆

⪏ῆ㠦㍲ 䦷㡆㦮 ゚ᾦ㥚䠮☚⓪ Ṗ㫇⩻㧊 㧞⓪ Table 3. The allele of apolipoprotein E and prevalence ratios of hypertension: Odds

ratios(95% confidence intervals)

A l l e l e U n a d j u s t e d Adjusted for Adjusted for age and sex various covariates*

ȿ3 /ȿ3 1 . 0 0 0 1 . 0 0 0 1 . 0 0 0

ȿ2 /ȿ2 3 . 0 1 1 ( 0 . 5 0 0 - 1 8 . 1 1 9 ) 4 . 5 0 5 ( 0 . 6 7 1 - 3 0 . 2 2 8 ) 5 . 7 3 7 ( 0 . 8 0 7 - 4 0 . 7 6 1 ) ȿ2 /ȿ3 0.892(0.599- 1.329) 0.847(0.544- 1.320) 0.936(0.595- 1.472) ȿ2 /ȿ4 1.606(0.428- 6.025) 1.152(0.284- 4.671) 1.205(0.297- 4.894) ȿ3 /ȿ4 0.059(0.703- 1.307) 0.829(0.586- 1.174) 0.794(0.559- 1.127) ȿ4 /ȿ4 0.365(0.080- 1.657) 0.370(0.075- 1.817) 0.285(0.056- 1.451)

* Adjusted for age, gender, total cholesterol, fasting blood sugar, BMI, smoking status, alcohol

drinking status and exercise status

╖㌗㧦Ṗ 㠜⓪ ╖㌗㧦㠦 ゚䟊 4⺆ ⏨Ợ ⋮䌖

⋲┺. 㧊ộ㦖 㧒⹮㧎ῂṖ ⁞㡆䞶 ➢ 2 - 4⎚㦮 㑮ⳛ㡆㧻㧊 ♲┺Ⳋ Ṗ㫇⩻㥶㩚㧦⯒ Ṗ㰚 ἶ㥚 䠮 ╖㌗ῆ㧊 ⁞㡆㦚 䞶 ➢⓪ 1 0 - 1 4⎚㦮 㑮ⳛ㡆 㧻㧊 Ṗ⓻䞮┺⓪ ộ㦚 㦮⹎䞲┺. 㧊 㤦䂯㦚 㩗 㣿䞮Ⳋ 㥶㩚㩗㦒⪲ Ṧ㑮㎇㧊 㧞⓪ ㌂⧢㠦 ╖ 䟊 ▪㤇 䢲⹲䞲 ㌳䢲㔋ὖ Ṳ㍶㌂㠛㦚 䞮㡂㟒 䞶 ộ㧊┺. ⡦䞲, 㥶㩚㣪㧎㦮 㡗䟻☚ 䢮㧦㦮 䢮 ἓ⏎㿲㌗䌲㠦 ➆⧒ ╂⧒㰚┺. 䡞㼃䢎⳾㔲㓺䕊 㧊 13-19 ືmol/L 㧊㌗㧊Ⳋ ὖ㌗☯ⰻἓ䢪㯳

⹲㌳㧊 㯳Ṗ䞮Ợ ♲┺. 䢎⳾㔲㓺䕊㦮 㥶⩻䞲 㥶㩚㧦 Methylenetetrahydrofolate Reductase ( M T H F R ) 㦖 ゚䌖⹒ ㎃䀾Ṗ ⿖㫇䞲 ἓ㤆㠦 䢎

⳾㔲㓺䕊ὒ ▪㤇 ὖ⩾㧊 㧞Ợ ♲┺. ⁎Ⰲἶ, 䙂 䢪㰖⹿㌆ὒ 䆲⩞㓺䎢⪺ ㎃䀾㦮 㩲䞲㦖 Ṗ㫇⩻

㥶㩚㧦⯒ Ṗ㰚 ㌂⧢㠦㍲⓪ 䡞㼃 䆲⩞㓺䎢⪺㦚

⌄㿪⓪ 䣾ὒṖ 㧞┺. 㔶㼊䢲☯, 㼊㭧Ṧ㏢, ╏␾

㡞⹿, 㔳㧊㎃䀾 ❇㦖 Ṗ㫇⩻ 㥶㩚㧦⯒ Ṗ㰚 䢮 㧦㠦Ợ ☚㤖㧊 ♲┺[31].

➆⧒㍲ 㥶㩚㣪㧎㧊 ▪ 㭧㣪䞲㰖 㞚┞Ⳋ 䢮 ἓ㣪㧎㧊 ▪ 㭧㣪䞲㰖⯒ 䘟Ṗ䞮ἶ, ⁎ ῂ㼊㩗 㧎 ⹲⼧₆㩚㦚 㧊䟊䞶 㑮 㧞┺Ⳋ 㤆Ⰲ⓪ 㰞⼧

⹲㌳㦚 㡞⹿䞮₆ 㥚䞲 ῂ㼊㩗㧎 㰖䂾㦚 Ṳ㧎

⼚⪲ 㩲㔲䞶 㑮 㧞㦚 ộ㧊┺. ἆῃ, 㠊⟺ 㰞⼧

㦮 ⹲㌳ὒ ὖ⩾♲ 䢮ἓ㣪㧎ὒ 㥶㩚㩗㧎 㣪㧎

✺㦮 ☛Ⱃ㩗㧎 㡗䟻㦚 䘟Ṗ䞮Ⳋ㍲ 㧊✺㦮 ㌗ 䢎㧧㣿㧊 㰞⼧⹲㌳㠦 ⹎䂮⓪ 㡗䟻㦚 㿪Ṗ䞲┺

Ⳋ 㫖 ▪ 㩫䢫䞮Ợ Ṳ㧎㩗㧎 㡞⹿╖㺛ὒ 䂮⬢

⹿⻫㦚 㩗㣿䞶 㑮 㧞㦚 ộ㧊┺.

殚 檃

APOE 㥶㩚㧦⓪ 㞢㸪䞮㧊Ⲏ ⼧㦮 㥶㩚㩗 㥚 䠮㧎㧦⪲ 㞢⩺㪎 㧞㦒Ⳇ, ☯ⰻἓ䢪, ὖ㌗☯ⰻ 㰞䢮 ❇㦮 㕂䡞ὖ㰞䢮ὒ ὖ⩾㧊 㧞┺ἶ 㞢⩺

㪎 㧞┺. ⽎ 㡆ῂ㠦㍲⓪ 㰖㡃㌂䣢 㧎ῂ⯒ ╖㌗

㦒⪲ ἶ䡞㞫 䢮㧦㠦㍲ APOE ┺䡫㎇㦮 ⿚䙂

⯒ 㞢㞚⽊ἶ, ἶ䡞㞫ὒ APOE ┺䡫㎇ ⿚䙂Ṗ 㡆ὖ㎇㧊 㧞⓪Ṗ⯒ 㫆㌂䞮ἶ㧦 䞮㡖┺.

2 0 0 5⎚ 1 0㤪 1 7㧒⿖䎆 1 1㤪 1 8㧒₢㰖 ㍺ⶎ㫆

㌂ ⹥ ỊṫỖ㰚㦚 㔲䟟䞲 2 0㎎ 㧊㌗ 㧎㻲ὧ㡃 㔲 㔲⹒㦚 ╖㌗㦒⪲ APOE ╖Ⱃ㥶㩚㧦㠦 ➆

⯎ ἶ䡞㞫㦮 㥶⼧⮶㦚 ㌆㿲䞮㡖ἶ, APOE㢖 ἶ䡞㞫ὒ㦮 ὖ⩾㎇㦖 ┺㭧 ⪲㰖㓺䕇 䣢‖⿚㍳

㦚 㧊㣿䞮㡂 ᾦ㹾゚㢖 95% 㔶⬆ῂṚ㦚 㩲㔲 䞮㡖┺.

ȿ2 /ȿ2㦮 ἶ䡞㞫 㥶⼧⮶㦖 60.0%, ȿ2 /ȿ3⓪ 30.8%, ȿ2 /ȿ4⓪ 44.4%, ȿ3 /ȿ3⓪ 33.3%, ȿ3 /ȿ4⓪ 32.3%, ȿ4 /ȿ4⓪ 1 5 . 4 %㧊㠞㦒Ⳇ, ╖Ⱃ㥶㩚㧦⼚

ἶ䡞㞫 㥶⼧㥾㦖 䐋Ἒ㩗㦒⪲ 㥶㦮䞲 㹾㧊Ṗ 㠜㠞┺. ⡦䞲 ȿ3 /ȿ3⯒ ₆㭖㦒⪲ 䞮㡂 ⪲㰖㓺䕇 䣢‖⿚㍳㦚 䞲 ἆὒ ἶ䡞㞫 㥶⼧⮶㦮 ᾦ㹾゚

⓪ ȿ2 /ȿ2Ṗ 5.737, ȿ2 /ȿ3Ṗ 0.936, ȿ2 /ȿ4Ṗ 1 . 2 0 5 , ȿ3 /ȿ4Ṗ 0.794, ⁎Ⰲἶ ȿ4 /ȿ4Ṗ 0 . 2 8 5㧊㠞㦒Ⳇ, A P O E㢖 ἶ䡞㞫㦖 䐋Ἒ㩗㦒⪲ 㥶㦮䞲 ὖ⩾㧊 㠜㠞┺.

➆⧒㍲ ἶ䡞㞫ὒ APOE ┺䡫㎇ ⿚䙂 ㌂㧊㠦 䐋Ἒ㩗㦒⪲ 㥶㦮䞲 ὖ⩾㎇㦚 ⽒ 㑮 㠜㠞┺.

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