Association of SNPs rs6498169 and rs10984447 with multiple sclerosis in Saudi patients: a model of the usefulness of familial aggregates in identifying genetic linkage in a multifactorial disease.

OBJECTIVE: Genome-Wide association studies (GWAS) showed an association between subset of single-nucleotide polymorphism (SNPs) and multiple sclerosis. Our study aims to study this association in Saudi familial multiple sclerosis patients. METHODS: Four subject groups were used in this study: sporadic MS (MS patients without family history), FMS (MS patients who have at least one family member diagnosed with MS), related controls (relatives of FMS patients who appear to be free of the disease) and independent controls (healthy volunteers). Subjects were genotyped for 15 SNPs. The variation in the genotype distribution was analyzed across study groups by using logistic regression. RESULTS: 342 subjects were included. 99 were in the sporadic MS group, 22 were FMS, 89 were related control, and 132 were independent control. SNPS rs3135388, rs7577363, rs1321172, rs6897932, rs6498169, rs12487066, and rs4763655were associated with MS when MS and independent control groups were compared. Same SNPS were identified but with stronger association when the FMS and independent control groups were compared. Finally, when the patients and the controls were selected from a much more homogenous genetic pool from which it would be expected that only SNPs highly linked to MS would persist, only two SNPs rs6498169[OR 4.26, CI (1.17 - 15.51)];, and rs10984447 [OR 13.63, CI(1.54, 120.83) ][were associated with MS. CONCLUSIONS: Our results suggest that using a more homogenous genetic pool of cases and controls could help to identify the most significant MS-associated SNPs. Our finding is in agreement with other studies including larger sample size and more diverse populations.

Familial multiple sclerosis: does consanguinity have a role?

Parental consanguinity (PC) may be a risk factor for familial multiple sclerosis (FMS) throughout inbred communities. The objective of this report was to estimate prevalence of FMS and rate of PC among FMS versus non-FMS patients. All Saudi MS patients were identified from our registry. The history of PC was analyzed as a case-control study. In total 141 MS patients were identified. Of these, 30 (21%) reported having at least one affected relative, 37.6% reported PC and 16% presented first-degree PC. In addition, FMS patients were more likely than non-FMS patients to report PC. In conclusion, FMS is prevalent among Saudi MS patients. MS patients with a history of PC were more likely to have FMS, suggesting a potential role of consanguinity.

Role of CT angiographic plaque morphologic characteristics in addition to stenosis in predicting the symptomatic side in carotid artery disease.

BACKGROUND AND PURPOSE: Atherosclerotic disease of the carotid artery is an important cause of ischemic stroke. We evaluated carotid plaque morphologic features by using CTA in addition to stenosis in the setting of symptomatic hemispheric TIA/stroke to identify factors that may predict plaque activity. MATERIALS AND METHODS: Six hundred seventy-three patients (408 men; ages, 18-91 years; mean, 65.8 +/- 15.2 years) presenting with hemispheric ischemic symptoms and having a CTA that included imaging of both carotid arteries within 24 hours were studied. Scans were interpreted for morphologic features, such as plaque length and width, attenuation, shape, surface, presence and degree of calcification, and ILT in addition to stenosis. RESULTS: Univariable analysis showed that carotid occlusions (P = .01, OR = 5.27), high-grade stenosis (70%-99%) (P = .06, OR = 1.8), and the presence of ILT (P = .01, OR = 4.33) were highly predictive of the symptomatic side. Smooth plaque (P = .01, OR = 0.73) and extensive calcification (P = .03, OR = 0.72) were more commonly associated with the asymptomatic side. There was no correlation between plaque hypoattenuation (P = .7, OR = 1.06) or ulcerated plaque (P = .74, OR = 0.955) in predicting the symptomatic side. In a multivariable logistic regression model, the presence of ILT was still found to be significantly associated with the symptomatic side (P = .048, OR = 3.1) and the presence of extensive calcification, with the asymptomatic carotid artery (P = .047, OR = 0.69). CONCLUSIONS: In addition to higher stenosis grades, the presence of ILT is highly predictive of the symptomatic side in carotid disease. Smooth plaque and extensive calcification seem to afford a protective effect. This information may be useful in radiologic risk stratification in carotid disease in addition to the current evidence available based on stenosis criteria alone.