LTA 252G allele containing haplotype block is associated with high serum C-reactive protein levels.
C-reactive protein (CRP), an inflammatory biomarker, is a predictor of future risk for cardiovascular disease. Hypothetically, the levels of inflammatory response to microbial and lifestyle-related factors are influenced by genetic factors. LT-alpha is a proinflammatory cytokine that plays an important role in the pathogenesis of atherosclerosis in mice. We examined the association between gene polymorphism of the LT-alpha coding gene, LTA A252G, and CRP based on a case-control study. The top 149 and bottom 151 subjects in terms of CRP levels were selected for genotyping from among 1000 A-bomb survivors free from acute infection, chronic liver diseases, uremia, autoimmune diseases, and cancers. The genotype of LTA was determined by fluorescence resonance energy transfer-polymerase chain reaction (FRET-PCR) and subsequent melting curve analysis. The values of traditional risk factors such as body mass index (BMI), white blood cell (WBC) count, hemoglobin (Hb) concentration, and glycated Hb (HbA1c) differed significantly between the low and high CRP groups. After adjusting for the effect of sex, age, BMI, WBC, Hb, and HbA1c, the LTA 252G allele was found to be associated with high CRP levels (odds ratio = 1.93, P = 0.007) by multiple logistic regression analysis. Thus, CRP levels are influenced not only by environmental factors but also by the polymorphism of LTA or other genes in the same haplotype block.
Suzuki
Gen
G
Department of Clinical Studies, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima 732-0815, Japan. gsuzuki@rerf.or.jp
Izumi
Shizue
S
Hakoda
Masayuki
M
Takahashi
Norio
N
D000483:Alleles; D001161:Arteriosclerosis / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D002097:C-Reactive Protein / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors
D008233:Lymphotoxin-alpha; D002097:C-Reactive Protein