Genetic Risk Factors for Perinatal Arterial Ischemic Stroke

Abstract

The cause of perinatal arterial ischemic stroke is unknown in most cases. We explored whether genetic polymorphisms modify the risk of perinatal arterial ischemic stroke. In a population-based case-control study of 1997–2002 births at Kaiser Permanente Northern California, we identified 13 white infants with perinatal arterial ischemic stroke. Controls included 86 randomly selected white infants. We genotyped polymorphisms in 9 genes involved in inflammation, thrombosis or lipid metabolism that have been previously linked with stroke, and compared genotype frequencies in case and control individuals. We tested the following polymorphisms: TNF-α-308, IL-6, lymphotoxin A, factor V Leiden, MTHFR 1298 and 667, prothrombin 20210, and apolipoprotein E ε2 and ε4 alleles. Patients with perinatal arterial ischemic stroke were more likely than controls to have at least one apolipoprotein E ε4 allele (54% vs. 25%, p=0.03). More patients with perinatal arterial ischemic stroke carried two ε4 alleles than did controls (15% vs. 2%, p=0.09), though this finding was not statistically significant. Proinflammatory and prothrombotic polymorphisms were not associated with perinatal arterial ischemic stroke in this small study. The apolipoprotein E polymorphism may confer genetic susceptibility for perinatal arterial ischemic stroke. Larger population-based studies are needed to confirm this finding.

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.…”

“…Tong et al 2010;Sultana et al 2011;Szabo and Acsady 2011;Cui et al 2012;Tuttolomondo et al 2012;Gelfand et al 2013;Ma 2012) reported G allele frequencies, with 13 studies of Asian adults, one of Asian children, seven of Caucasian adults, and two of Caucasian children.…”

Is the 1298A>C polymorphism in the MTHFR gene a risk factor for arterial ischaemic stroke in children? The results of meta-analysis

“…1. Finally, eight case-control studies were included in the meta-analysis with a total number of 426 paediatric patients with AIS and 778 control subjects [12][13][14][20][21][22][23][24].…”

“…Caucasians were the most common race. In order to genotype the MTHFR 1298A>C polymorphism, PCR-RFLP analysis was used in four of the studies [12,13,20,21], CVD StripAssays in two studies [14,22] and Taqman PCR in one study [23]. The genotyping method was not specified in one of the studies [24].…”

“…The genotyping method was not specified in one of the studies [24]. The largest groups of AIS patients were recruited by Balcerzyk et al [12], Herak et al [14] and Komitopoulou et al [22], whereas the fewest patients were recruited by Gelfand et al [23] and Morita et al [24]. The largest group of control subjects was analysed in the study by Sirachainan et al [21] and the lowest one in the study by Biswas et al [13].…”