Association between Tumor Necrosis Factor-Alpha (–308G→A and –238G→A) Polymorphisms and Homocysteine Levels in Patients with Ischemic Strokes and Silent Brain Infarctions

Abstract

Background and Purpose: The aims of this study were to evaluate the role of tumor necrosis factor-α (TNF-α) polymorphisms in patients susceptible to ischemic stroke and silent brain infarction (SBI), and to determine the relationship between TNF-α polymorphisms and plasma total homocysteine (tHcy) levels. Methods: We studied 237 patients with ischemic stroke, 257 patients with SBIs, and 216 control subjects. For control subjects, we selected healthy individuals matched for gender and age from those individuals who came to our hospital for health examinations. The TNF-α–308G→A and –238G→A genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Results: The frequency of the TNF-α–308G→A polymorphism was significantly different between the patients with ischemic stroke and the control group (GG vs. GA+AA; adjusted odds ratio, AOR, 0.50; 95% CI 0.255–0.989). By subgroup analysis, when tHcy levels were stratified into high (>10.80 µmol/l), moderate (8.21–10.80 µmol/l), and low levels (<8.21 µmol/l), the frequency of the TNF-α–308GA+AA genotype in the highest tertile group was higher than in the lowest tertile group (AOR 2.46; 95% CI 1.063–5.699). However, the relationship between SBI susceptibility and polymorphisms of TNF-αwas not established. The tHcy levels were significantly and inversely correlated with folate levels in the TNF-α–308GG and TNF-α–238GG genotypes in the ischemic stroke, SBI, and control groups (p< 0.05). Conclusions: Our results suggest that the TNF-α–308G→A polymorphism is responsible for susceptibility to ischemic stroke and is associated with high tHcy levels in Koreans.

The IL6 gene polymorphism −634C>G and IL17F gene polymorphism 7488T>C influence bone mineral density in young and elderly Japanese women

“…The genotypes of IL6 −634C>G (rs1800796), TNFα −308G>A (rs1800629), IL17F 7488T>C (rs763780), TGFβ 869T>C (rs1800470), OPG 163A>G (rs3102735) and MTHFR 677C>T (rs1801133) (Jørgensen et al, 2004;Kawaguchi et al, 2006;Kim et al, 2010;Lario et al, 1999;Miyao et al, 2000;Ota et al, 2001;Seiderer et al, 2008) were analyzed by the polymerase chain reaction (PCR)-RFLP method. Genomic DNA was isolated from the fingernail using a DNA isolation kit (Nippon Gene Co., Ltd, Tokyo, Japan).…”

“…The 60 bp fragment represents the (−634)G allele (Ota et al, 2001). Digestion of the PCR products of TNFα with NcoI generates two fragments of 87 and 20 bp in length; the (−308)A allele remained uncut with a length of 107 bp (Kim et al, 2010). Digestion of the PCR products of IL17F with NlaIII generated two fragments of 288 and 124 bp in length.…”

Systematic Review by Multivariate Meta-analyses on the Possible Role of Tumor Necrosis Factor-α Gene Polymorphisms in Association with Ischemic Stroke

“…Figure 1 shows the results of literature search and selection. A total of 186 articles were retrieved with the comprehensive literature search, and finally 25 articles (Bai and Cheng 2004;Balding et al 2004;Lee et al 2004;Um and Kim 2004;Karahan et al 2005;Rubattu et al 2005;Harcos et al 2006;Lalouschek et al 2006;Llamas Sillero et al 2007;Zhang et al 2007;Liu et al 2009Liu et al , 2012Shi et al 2009;Kim et al 2010;Tong et al 2010;Markoula et al 2011;Munshi et al 2011;Sultana et al 2011;Szabo and Acsady 2011;Wu et al 2011;Cui et al 2012;Tuttolomondo et al 2012;Gelfand et al 2013;Ma 2012) (18 in English and seven in Chinese) of them were included in the present study according to the eligible criteria. Forty-nine eligible case-control studies from these 25 articles involve 23 studies of -308G/A (6220 patients and 6531 controls), 14 studies of -238G/A (4760 patients and 4389 controls), four studies of -857C/T (2589 patients and 2097 controls), three studies of -1031T/C (2416 patients and 1948 controls), one study (404 patients and 415 controls) of -244G/ A and -367G/A, one study (67 patients and 70 controls) of -646G/A, -806C/T, -863C/A, and one study (525 patients and 500 controls) of ?448G/A.…”

“…Fourteen case-control studies from 11 articles (Lalouschek et al 2006;Llamas Sillero et al 2007;Liu et al 2009;Shi et al 2009;Kim et al 2010;Tong et al 2010;Wu et al 2011;Cui et al 2012;Liu et al 2012;Ma 2012) reported the frequency of -238G/A polymorphism, 11 studies of Asian adults, one of Asian children, and two of Caucasian adults. Three studies (Cui et al 2012;Liu et al 2012;Ma 2012) of Asian adults did not observe HWE in controls.…”

Association between common genetic variants of α2A-, α2B- and α2C-adrenoceptors and the risk of silent brain infarction

“…Transverse T1-weighted, T2-weighted, and fluid-attenuated inversion recovery (FLAIR) images were obtained with a slice thickness of 7 mm. SBI was diagnosed based on the following criteria (17,18): i) Spotty areas ≥3 mm in diameter in the area supplied by deep perforating arteries, showing high intensity in the T2 and FLAIR images and low intensity in the T1 image; ii) absence of neurological symptoms corresponding to the MRI lesions; iii) no history of clinical stroke, including transient ischemic attack; iv) no prior ischemic heart disease; v) ≥40 years of age and vi) Korean descendance (residency in Seoul or Kyeonggi, South Korea). Among the initial 1,000 participants evaluated, 191 met the exclusion criteria, leaving 448 controls and 361 cases.…”