Clinical factors such as B-type natriuretic peptide link to factor VII, endothelial NO synthase and estrogen receptor alpha polymorphism in elderly women.
OBJECTIVE
This study evaluated the presence of genetic mutations in relation to thrombosis or atherosclerosis in elderly women.


METHODS
This is an observational study of 93 Japanese women with a mean age of 80.9 years recruited from outpatient clinics of Nagoya University and its related hospitals. Ten single nucleotide polymorphisms (SNPs) were studied. Each gene studied acts in or is related to either blood coagulation (factor V Leiden, prothrombin G20210A, factor XIII Val34Leu, factor VII Arg353Gln, MTHFR C677T, beta-fibrinogen G-455A, PAI-1 4G/5G), metabolic syndrome-related pathways (PPARalpha Leu162Val), or endothelium/estrogen system (eNOS Glu298Asp, ERalpha IVS1-401). SNPs were analyzed for their relation to clinical values including lipids, B-type natriuretic peptide (BNP), fasting plasma glucose, tumor necrosis factor-alpha, interleukin-6, cyclic GMP, and nitric oxide metabolites.


RESULTS
Comparisons between the distributions of different genotypes and clinical values showed three relationships. First, factor VII Arg353Gln and HDL-cholesterol (HDL-C) were linked to Arg/Arg carriers at higher levels (P=.049). The HDL-C to LDL-cholesterol ratio supported this link (P=.027). Second, eNOS Glu298Asp and triglycerides were linked to Glu/Glu carriers at higher levels (P=.031). Third, ERalpha IVS1-401 and BNP were related to CC genotype at lower levels (P=.031). Additionally, the last two relations showed that genotype does not influence the demarcation line of biomarkers, but the plasma/serum levels of biomarkers instead.


CONCLUSIONS
Correlations of factor VII Arg353Gln with HDL-C and eNOS Glu298Asp with triglycerides are new findings. Polymorphisms in the endothelium/estrogen system and the heart failure marker BNP are also correlated, with ERalpha IVS1-401 being the first identified marker. SNPs may be helpful for understanding the pathophysiology of atherosclerotic diseases in elderly women.
Funami
Jun
J
Department of Geriatrics, Nagoya University Graduate School of Medicine, Tsuruma-cho 65, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Hayashi
Toshio
T
Nomura
Hideki
H
Ding
Qun-Fang
QF
Ishitsuka-Watanabe
Asako
A
Matsui-Hirai
Hisako
H
Ina
Koichiro
K
Zhang
Jie
J
Yu
Ze-Yun
ZY
Iguchi
Akihisa
A
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics; D005167:Factor VII / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D013927:Thrombosis / Q000097:blood / Q000235:genetics*
D047628:Estrogen Receptor alpha; D020097:Natriuretic Peptide, Brain; D005167:Factor VII; D004247:DNA; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III