Associations of a polymorphism in the intercellular adhesion molecule-1 (ICAM1) gene and ICAM1 serum levels with migraine in a Chinese Han population
Introduction
Although the pathogenesis of migraine is not clearly understood, a number of recent studies have implicated genetic susceptibility to neurogenic inflammation factors in the etiology of this common disorder [1], [2], [3]. The −308A allele of the tumor necrosis factor-α (TNFA) gene, for example, has been associated with increased TNFα levels in female cases of migraine without aura (MOA) [4], and convincing evidence exists that the TNFα plays an important role in inflammatory hyperalgesia [5]. Moreover, studies indicate that, compared with controls, the frequency of the + 3953 T allele of the gene encoding interleukin-1β (IL1B) is significantly higher in cases of MOA [6]. Similarly, a variety of reports have identified associations between polymorphisms in the IL1, IL4, IL10, IL13, 5-HT1A and 5-HT1B genes and migraine [7], [8], [9]. Collectively these data indicate that single nucleotide polymorphism analysis of candidate genes can assist in the diagnosis of migraine, as well as opening up the possibility of gene therapy for this disorder [10].
ICAM1 is an inflammatory cytokine that mediates cell–cell and cell–extracellular matrix interactions, and that plays an important role in the pathogenesis of inflammatory or immune-related diseases. A series of studies have demonstrated associations between the ICAM1 G241R and K469E polymorphisms and inflammatory and immune disorders [11], [12], [13], as well as coronary artery calcification, biliary atresia and ischemic stroke [14], [15], [16]. Despite the fact that ICAM1 has been implicated in the pathogenesis of migraine, however [17], [18], [19], there have been no such studies on the correlation between ICAM1 gene polymorphisms and susceptibility to migraine. Accordingly, we designed a case–control study to evaluate the association between the frequency distribution of alleles of the ICAM1 G241R and K469E polymorphic loci and migraine susceptibility, and to determine the relationship between these polymorphisms and serum levels of ICAM1.
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Source and grouping
Subjects were from the Han Chinese population and were divided into a migraine group and a control group. The migraine group consisted of 114 individuals (61 females, 42 males; mean age 38.9 years, range 13–60 years) consecutively diagnosed with migraine at the People's Hospital of Liaoning Province between March 2011 to December 2012, of which 80 were MOA and 34 were migraine with aura (MA). The control group consisted of 125 healthy age- and gender-matched volunteers and workers at the People's
K469E genotypes
Enzyme-digested PCR amplification products for the K469E genotypes were as follows: E/E (two bands at 136 bp and 87 bp), K/E (three bands at 223 bp, 36 bp and 87 bp) and K/K (single band at 223 bp) (Fig. 1).
G241R genotypes
Enzyme-digested PCR amplification products for the G241R genotypes were as follows: G/G (single band at 212 bp one band). No other genotypes were detected (Fig. 2).
Genomic DNA sequencing
Sequencing results of the K469E (Fig. 3) and G241R (Fig. 4) samples were consistent with the results of the enzyme-digested PCR
Discussion
Migraine is a common disease of the central nervous system (CNS) characterized by primary headache recurrent with unilateral or bilateral throbbing pain, of which MA and MOA are the two most common subtypes. Although family heredity, cerebral vasospasm, nerve function disorder and neurogenic inflammation are known to contribute to migraine, its exact pathogenesis is unclear [22], [23], [24]. The neurogenic inflammation theory of migraine has its anatomical basis in the trigeminal vascular
Conflicts of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
Ethical standard
This study was carried in accordance with ethical standards as set out in the Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study.
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2020, Progress in Brain ResearchCitation Excerpt :Of note, the cortical inflammatory response following CSD could be blunted in IL-1 receptor-1 knockout mice and suppressed by dexamethasone (Takizawa et al., 2020). In migraineurs, whether there is an increase in blood cytokine level is controversial (Table 2) (Duarte et al., 2015; Empl et al., 2003; Fidan et al., 2006; Han, 2019; He et al., 2014; Kocer et al., 2009; Martami et al., 2018; Oliveira et al., 2017; Perini et al., 2005; Sarchielli et al., 2004, 2006; Tanure et al., 2010; Uzar et al., 2011; Van Hilten et al., 1991; Wang et al., 2015; Yucel et al., 2016). There are reports stating that inflammatory markers increase in the ictal and the interictal phases of migraine; however, other studies have reported no change during the ictal and interictal phases or even a decrease during interictal phase.
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2016, Journal of the Neurological SciencesAssociation of ICAM-1 K469E polymorphism with dengue infection in North Indian population
2016, Microbial PathogenesisCitation Excerpt :When we evaluated the expression of ICAM-1 mRNA with different genotypes in DHF/DSS patients, we found significantly higher levels of ICAM-1 mRNA in homozygous genotype (EE). Our ICAM-1 mRNA expression results are in concordance with previous studies which showed that K469E genotype was associated with higher serum level of ICAM-1 mRNA in migraine [30]. Another study revealed that E allele induces cell surface expression of ICAM-1, which in turn leads to greater adhesion of leukocytes to damaged endothelium [38].