Association of AMPK Pathway-Related Gene Polymorphisms with Symptomatic Intracranial Atherosclerotic Stenosis in a Chinese Han Population.

Background and Objective: Recently, AMP-activated protein kinase (AMPK) signaling was confirmed to be intimately associated with atherosclerosis. Evidence indicates that genetic susceptibility plays an important role in the etiology of symptomatic intracranial atherosclerotic stenosis (sICAS), and few genes have been pinpointed as responsible. This study investigated possible links between single nucleotide polymorphisms (SNPs) of AMPK-related genes and sICAS in Han Chinese subjects. Methods: Target gene sequencing was carried out in 400 sICAS Han Chinese patients and 1007 healthy controls for 11 AMPK pathway-related genes. Chi-squared testing and multiple logistic regression in dominant, recessive, and additive models were used to evaluate the association between SNPs and risk of sICAS. Bonferroni corrections were performed with a p < (0.05/44 = 0.0011) as statistically significant. Further subgroup data analyses was conducted using chi-squared or t-tests. Results: There were 44 common variants of 11 candidate genes distributed differently between sICAS patients and healthy controls, among which the INSR rs78312382 SNP remained significant even after a Bonferroni correction. Logistic regression analysis showed that rs78312382 was significantly associated with the risk of sICAS in both dominant and additive models (p(Bonferroni) = 7.874e(-5) and 0.000506, respectively), with the A allele being much more prevalent in the sICAS group (p = 0.000404). Conclusions: Variants of the INSR rs78312382 loci may play an important role in the development of sICAS among in Han Chinese populations. Furthermore, the A allele at this locus may be a risk factor and potential biomarker of genetic risk for this illness.