Apolipoprotein A5 gene promoter region T-1131C polymorphism associates with elevated circulating triglyceride levels and confers susceptibility for development of ischemic stroke

被引:55
作者
Havasi, Viktoria
Szolnoki, Zoltan
Talian, Gabor
Bene, Judit
Komlosi, Katalin
Maasz, Anita
Somogyvari, Ferenc
Kondacs, Andras
Szabo, Mihaly
Fodor, Lajos
Bodor, Anita
Melegh, Bela [1 ]
机构
[1] Univ Pecs, Dept Med Genet & Child Dev, H-7622 Pecs, Hungary
[2] Pandy Kalman Cty Hosp, Dept Neurol & Neurophysiol, Gyula, Hungary
[3] Univ Pecs, Hungarian Acad Sci, Clin Genet Res Grp, MTA PTE, H-7622 Pecs, Hungary
[4] Pandy Kalman Cty Hosp, Cent Lab, Gyula, Hungary
[5] Univ Szeged, Fac Med, Dept Clin Microbiol, H-6720 Szeged, Hungary
[6] Rethy Pal Cty Hosp, Dept Pathol, Bekescsaba, Hungary
关键词
apoA5-1131C; triglycerides; stroke; peroxisome proliferator-activated receptor; PPAR;
D O I
10.1385/JMN:29:2:177
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The possible pathogenic role of triglycerides (TG) in the development of ischemic stroke is still under extensive investigation. Recently, apolipoprotein (apo)A5 gene promoter region T-1131C polymorphism has been shown to associate with elevated serum TG levels. In the current work, a total of 302 subjects were classified as being large vessel-associated, small vessel-associated, or belonging to a mixed group of ischemic stroke-affected patients. The level of TG was increased in all groups (p < 0.01). The apoA5-1131C allele frequency was approximately twofold in all groups of stroke patients compared with the controls (5 vs 10-12%; p < 0.05); and the apoA5-1131C allele itself was also found to associate with increased TG levels in all groups. In a multivariate logistic regression analysis model adjusted for differences in age, gender, serum cholesterol, hypertension, presence of diabetes mellitus, smoking and drinking habits, and ischemic heart disease, a significantly increased risk of developing stroke disease was found in patients carrying the apoA5-1131C allele (p < 0.05; odds ratio OR = 2.1 [1.3-4.7]); this association was also proven for all subtypes of the stroke. The results presented here suggest that the apoA5-1131C allele is an independent risk factor for the development of stroke. Being that apoA5 gene is under the control of the peroxisome proliferator-activated receptor a, theoretically, the current observations also can have long-term therapeutic consequences.
引用
收藏
页码:177 / 183
页数:7
相关论文
共 38 条
[1]   Broad and narrow heritabilities of quantitative traits in a founder population [J].
Abney, M ;
McPeek, MS ;
Ober, C .
AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 68 (05) :1302-1307
[2]   Structure-function studies of human apolipoprotein A-V: A regulator of plasma lipid homeostasis [J].
Beckstead, JA ;
Oda, MN ;
Martin, DDO ;
Forte, TM ;
Bielicki, JK ;
Berger, T ;
Luty, R ;
Kay, CM ;
Ryan, RO .
BIOCHEMISTRY, 2003, 42 (31) :9416-9423
[3]   A single nucleotide polymorphism-113 IT &gt; C in the apolipoprotein A5 gene is associated with an increased risk of coronary artery disease and alters triglyceride metabolism in Chinese [J].
Bi, N ;
Yan, SK ;
Li, GP ;
Yin, ZN ;
Chen, BS .
MOLECULAR GENETICS AND METABOLISM, 2004, 83 (03) :280-286
[4]   Association between impaired insulin sensitivity and stroke [J].
Bravata, DM ;
Wells, CK ;
Kernan, WN ;
Concato, J ;
Brass, LM ;
Gulanski, BI .
NEUROEPIDEMIOLOGY, 2005, 25 (02) :69-74
[5]   Genetic susceptibility and ischaemic stroke [J].
Elbaz, A ;
Amarenco, P .
CURRENT OPINION IN NEUROLOGY, 1999, 12 (01) :47-55
[6]   Association found between the promoter region polymorphism in the apolipoprotein A-V gene and the serum triglyceride level in Japanese schoolchildren [J].
Endo, K ;
Yanagi, H ;
Araki, J ;
Hirano, C ;
Yamakawa-Kobayashi, K ;
Tomura, S .
HUMAN GENETICS, 2002, 111 (06) :570-572
[7]   Mechanism of triglyceride lowering in mice expressing human apolipoprotein A5 [J].
Fruchart-Najib, J ;
Baugé, E ;
Niculescu, LS ;
Pham, T ;
Thomas, B ;
Rommens, C ;
Majd, Z ;
Brewer, B ;
Pennacchio, LA ;
Fruchart, JC .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 319 (02) :397-404
[8]   Lipids and stroke - A paradox resolved [J].
Hachinski, V ;
Graffagnino, C ;
Beaudry, M ;
Bernier, G ;
Buck, C ;
Donner, A ;
Spence, JD ;
Doig, G ;
Wolfe, BMJ .
ARCHIVES OF NEUROLOGY, 1996, 53 (04) :303-308
[9]   RISK-FACTORS OF STROKE INCIDENCE AND MORTALITY - A 12-YEAR FOLLOW-UP OF THE OSLO STUDY [J].
HAHEIM, LL ;
HOLME, I ;
HJERMANN, I ;
LEREN, P .
STROKE, 1993, 24 (10) :1484-1489
[10]   Genetics and ischaemic stroke [J].
Hassan, A ;
Markus, HS .
BRAIN, 2000, 123 :1784-1812