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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
2013

A nonsense polymorphism (R392X) in TLR5 protects from obesity but predisposes to diabetes

The TLR5 gene encodes an innate immunity receptor. Mice lacking Tlr5 (T5KO) develop insulin resistance and increased adiposity. Owing to the segregation of a dominant nonsense polymorphism (R392X, rs5744168), a portion of humans lack TLR5 function. We investigated whether the nonsense polymorphism influences obesity and susceptibility to type 2 diabetes (T2D). R392X was genotyped in two cohorts from Saudi Arabia, a region where obesity and type 2 diabetes (T2D) are highly prevalent. The nonsense allele was found to protect from obesity (p(combined) = 0.0062; odds ratio, 0.51) and to associate with lower body mass index (BMI) (p(combined) = 0.0061); this allele also correlated with a reduced production of proinflammatory cytokines. A significant interaction was noted between rs5744168 and sex in affecting BMI (p(interaction) = 0.006), and stratification by gender revealed that the association is driven by females (p(combined) = 0.0016 and 0.0006 for obesity and BMI, respectively). The nonsense polymorphism also associated with BMI in nonobese women. After correction for BMI, the 392X allele was found to represent a risk factor for T2D with a sex-specific effect (p(interaction) = 0.023) mediated by females (p = 0.021; odds ratio, 2.60). Fasting plasma glucose levels in nondiabetic individuals were also higher in women carrying the nonsense allele (p = 0.012). Thus, in contrast to T5KO mice, loss of human TLR5 function protects from weight gain, but in analogy to the animal model, the nonsense allele predisposes to T2D. These effects are apparently sex-specific. Data in this study reinforce the hypothesis that metabolic diseases, including T2D, are associated with immune dysregulation.

نوع عمل المنشور
Observational
رقم المجلد
190
رقم الانشاء
7
مجلة/صحيفة
Journal of Immunology 2013
الصفحات
3716-3720
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