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Shaun Sabico

Assistant Professor

Assistant Professor and Deputy Director

كلية العلوم
Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, KSU
المنشورات
مقال فى مجلة
2012

Mammalian NPC1 genes may undergo positive selection and human polymorphisms associate with type 2 diabetes

BACKGROUND:

The NPC1 gene encodes a protein involved in intracellular lipid trafficking; its second endosomal loop (loop 2) is a receptor for filoviruses. A polymorphism (His215Arg) in NPC1 was associated with obesity in Europeans. Adaptations to diet and pathogens represented powerful selective forces; thus, we analyzed the evolutionary history of the gene and exploited this information for the identification of variants/residues of functional importance in human disease.

METHODS:

We performed phylogenetic analysis, population genetic tests, and genotype-phenotype analysis in a population from Saudi Arabia.

RESULTS:

Maximum-likelihood ratio tests indicated the action of positive selection on loop 2 and identified three residues as selection targets; these were confirmed by an independent random effects likelihood (REL) analysis. No selection signature was detected in present-day human populations, but analysis of nonsynonymous polymorphisms showed that a variant (Ile642Met, rs1788799) in the sterol sensing domain affects a highly conserved position. This variant and the previously described His215Arg polymorphism were tested for association with obesity and type 2 diabetes (T2D) in a cohort from Saudi Arabia. Whereas no association with obesity was detected, 642Met allele was found to predispose to T2D. A significant interaction was noted with sex (P = 0.041), and stratification on the basis of gender indicated that the association is driven by men (P = 0.0021, OR = 1.5). Notably, two NPC1 haplotypes were also associated with T2D in men (rs1805081-rs1788799, His-Met: P = 0.0012, OR = 1.54; His-Ile: P = 0.0004, OR = 0.63).

CONCLUSIONS:

Our data indicate a sex-specific effect of NPC1 variants on T2D risk and describe putative binding sites for filoviruses entry.

نوع عمل المنشور
Cross-sectional
رقم المجلد
10
مجلة/صحيفة
BMC Medicine 2012
الصفحات
140
مزيد من المنشورات
publications

Hyperglycemia associated with prediabetes (PD) alters NLRP3 inflammasome activity and related interleukins, yet no study has evaluated the expression of the NLRP3 inflammasome complex and related…

بواسطة Alfadul H, Sabico S, Alnaami AM, Amer OE, Hussain SD, Wani K, Clerici M, Al-Daghri NM
2023
تم النشر فى:
MDPI
publications

Objectives

بواسطة Aljuraiban GS, Algabsani S, Sabico S, Alshammari S, Aljazairy E, Al-Musharaf S
2023
تم النشر فى:
Elsevier
publications

The Metabolically Healthy Obese (MHO) is a unique phenotype of obesity in which individuals match the operational definition of obesity but do not display metabolic complications. Given this…

بواسطة Kaiser Wani , Balvir Kumar , Iram Saba , Shaun Sabico
2023
تم النشر فى:
Biolife Sas