Homogeneous assay of rs4343, an ACE I/D proxy, and an analysis in the British Women's Heart and Health Study (BWHHS)

被引：22

作者：

Abdollahi, Mohammad Reza ^{[1
,5
]}

Huang, Shuwen ^{[2
]}

Rodriguez, Santiago ^{[1
]}

Guthrie, Philip Alexander Isles ^{[1
]}

Smith, George Davey ^{[3
]}

Ebrahim, Shah ^{[4
]}

Lawlor, Debbie A. ^{[3
]}

Day, Ian N. M. ^{[1
]}

Gaunt, Tom R. ^{[1
]}

机构：

[1] Univ Bristol, Bristol Genet Epidemiol Lab, Bristol BS8 1TQ, Avon, England

[2] Southampton Gen Hosp, Div Human Genet, Southampton S016 6YD, Hants, England

[3] Dept Social Med, Bristol BS8 2PR, Avon, England

[4] Univ London London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1E 7HT, England

[5] Univ Leeds, St James Hosp, Genet Sect, Leeds Inst Mol Med, Leeds LS9 7TF, W Yorkshire, England

来源：

DISEASE MARKERS | 2008年 / 24卷 / 01期

基金：

英国医学研究理事会;

关键词：

angiotensin converting enzyme; insertion deletion polymorphism; metabolic syndrome trait; Alu element; single nucleotide polymorphism;

D O I：

10.1155/2008/813679

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Current literature suggests that ACE SNP rs4343, ACE 2350A> G in exon 17, T202T, may be the best proxy for the ACE Alu I/D whereas rs4363 and rs4362 may be slightly stronger predictors of ACE levels. Considering reported difficulties in genotyping ACE I/D and stronger associations of rs4343 than ACE I/D with plasma ACE levels in Africans, and suitability of rs4343 for allelic mRNA (cDNA) studies, we developed and validated a liquid phase assay for rs4343, which has advantage on both functional and technical grounds. We confirmed that rs4343, is in near perfect linkage disequilibrium (D' = 1, r(2) = 0.88, n = 64) with ACE I/D in Europeans (A and G alleles of rs4343 marking insertion and deletion alleles of ACE I/D respectively). We then studied its association with metabolic and cardiovascular traits in 3253 British women (60-79 years old). Apart from a nominal trend of association with diastolic blood pressure (p anova = 0.08; p trend = 0.05), no other associations were observed. A post-hoc vascular and general phenome scan revealed no further associations. We conclude that ACE I/D is not a major determinant of metabolic and cardiovascular traits in this population. Liquid phase genotyping of SNP rs4343 may be preferable to gel based ACE I/D genotyping both for technical and functional reasons.

引用

页码：11 / 17

页数：7

共 49 条

[11] Meta-analysis of association of insertion/deletion polymorphism of angiotensin I-converting enzyme gene with diabetic nephropathy and retinopathy [J].

Fujisawa, T ;

Ikegami, H ;

Kawaguchi, Y ;

Hamada, Y ;

Ueda, H ;

Shintani, M ;

Fukuda, M ;

Ogihara, T .

DIABETOLOGIA, 1998, 41 (01) :47-53

[12]

Huang XH, 1997, CLIN CHEM, V43, P2195

[13] Fast 5-hour determination of angiotensin-converting enzyme genotypes from blood by SDS-PAGE using PhastSystem [J].

Huang, XH ;

Koivula, T ;

Ilveskoski, E ;

Karhunen, PJ ;

Rantalaiho, V ;

Wirta, O ;

Pasternack, A ;

Lehtimaki, T .

CLINICA CHIMICA ACTA, 1997, 264 (01) :57-64

[14] The search for genenotype/phenotype associations and the phenome scan [J].

Jones, R ;

Pembrey, M ;

Golding, J ;

Herrick, D .

PAEDIATRIC AND PERINATAL EPIDEMIOLOGY, 2005, 19 (04) :264-275

[15] Measured haplotype analysis of the angiotensin-I converting enzyme gene [J].

Keavney, B ;

McKenzie, CA ;

Connell, JMC ;

Julier, C ;

Ratcliffe, PJ ;

Sobel, E ;

Lathrop, M ;

Farrall, M .

HUMAN MOLECULAR GENETICS, 1998, 7 (11) :1745-1751

[16]

Keavney B, 2000, LANCET, V355, P434

[17] Haplotypes extending across ACE are associated with Alzheimer's disease [J].

Kehoe, PG ;

Katzov, H ;

Feuk, L ;

Bennet, AM ;

Johansson, B ;

Wiman, B ;

de Faire, U ;

Cairns, NJ ;

Wilcock, GK ;

Brookes, AJ ;

Blennow, K ;

Prince, JA .

HUMAN MOLECULAR GENETICS, 2003, 12 (08) :859-867

[18] MALE-FEMALE DIFFERENCES IN FERTILITY AND BLOOD-PRESSURE IN ACE-DEFICIENT MICE [J].

KREGE, JH ;

JOHN, SWM ;

LANGENBACH, LL ;

HODGIN, JB ;

HAGAMAN, JR ;

BACHMAN, ES ;

JENNETTE, JC ;

OBRIEN, DA ;

SMITHIES, O .

NATURE, 1995, 375 (6527) :146-148

[19] The association of the PONI Q192R polymorphism with coronary heart disease:: findings from the British Women's Heart and Health cohort study and a meta-analysis -: art. no. 17 [J].

Lawlor, DA ;

Day, INM ;

Gaunt, TR ;

Hinks, LJ ;

Briggs, PJ ;

Kiessling, M ;

Timpson, N ;

Smith, GD ;

Ebrahim, S .

BMC GENETICS, 2004, 5 (1)

[20]

Lee YH, 2006, J RHEUMATOL, V33, P698

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