Role of SLMAP genetic variants in susceptibility of diabetes and diabetic retinopathy in Qatari population

Upadhyay, Rohit; Robay, Amal; Fakhro, Khalid; Khadil, Charbel Abi; Zirie, Mahmoud; Jayyousi, Amin; Elshafei, Maha; Kiss, Szilárd; D’Amico, Donald J.; Salit, Jacqueline; Staudt, Michelle R.; O’Beirne, Sarah L.; Chen, Xiaoliang; Tuana, Balwant S.; Crystal, Ronald G.; Ding, Hong

doi:10.1186/s12967-015-0411-6

Cited by 14 publications

(12 citation statements)

References 38 publications

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“…This trend has changed over the last 50 years. Females were more likely to be diagnosed with T2DM in recent years, associated with increasingly sedentary lifestyles and high energy, carbohydrate fatty diets . Consistent with prior studies, the current investigation found that African Americans and Hispanics were more likely to have an onset of T2DM than Caucasians in the Medicare population …”

Section: Discussionsupporting

confidence: 87%

Statins are associated with new onset type 2 diabetes mellitus (T2DM) in Medicare patients ≥65 years

Tangelloju

Little

Esterhay

et al. 2020

Diabetes Metabolism Res

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Background To evaluate the association of statins and co‐morbidities with new onset type 2 diabetes mellitus (T2DM) in patients 65 years and older. Methods This retrospective study used de‐identified administrative healthcare claims and enrolment data from a Medicare Advantage Prescription Drug (MAPD) health plan offered by a large multistate healthcare company. The plan covered >2.4 million individuals, of whom >1.7 million individuals were ≥65 years. Of these, 265 554 individuals had continuous MAPD enrolment January 2008 to December 2015. The unadjusted model assessed demographic, pharmacy and T2DM co‐morbidities as covariates. Significant variables (P < .05) in the unadjusted model were then included in the adjusted model. The adjusted model used Cox proportional hazards to evaluate covariate effects. Matched propensity score analysis was used to analyse the association of statins and T2DM onset. Results The cumulative rate of diagnosed T2DM onset in the study cohort was 4.82% (4314/89 390). Annualised incidence of T2DM diagnosis was 0.82%, 0.88%, 1.04% and 2.09% in 2012, 2013, 2014 and 2015, respectively. T2DM onset was associated with male sex, non‐white (African American or Hispanic ethnicity), statin use, hypertension, hyperlipidaemia, heart failure, lower limb ulceration, atherosclerosis, other retinopathy, angina pectoris, poor vision and blindness and absence ischaemic heart disease (IHD). Matched propensity score analysis showed that statin use was significantly associated with T2DM onset (Odds Ratio = 1.26, 95% Confidence Interval: 1.12‐1.41, P < .0001) in the adjusted model. Conclusions Analyses indicated that statin usage was associated with new onset T2DM after adjusting for covariates.

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Section: Discussionsupporting

confidence: 87%

Statins are associated with new onset type 2 diabetes mellitus (T2DM) in Medicare patients ≥65 years

Tangelloju

Little

Esterhay

et al. 2020

Diabetes Metabolism Res

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“…This trend has changed over the last 50 years. Previously, females were more likely to have diagnosed T2DM, but in recent years, the increasing sedentary lifestyle of males is attributed to their increased prevalence of T2DM (28, 29). In line with these studies the current study found that females were more likely to have a T2DM “remission” compared to males.…”

Section: Discussionmentioning

confidence: 99%

Type 2 Diabetes Mellitus (T2DM) “Remission” in Non-bariatric Patients 65 Years and Older

Tangelloju

Little

Esterhay

et al. 2019

Front. Public Health

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Objective: To analyze the factors associated with type 2 diabetes mellitus (T2DM) “remission” in non-bariatric Medicare patients 65 years and older. Research Design and Methods: A retrospective cohort analysis of a Medicare Advantage health plan was conducted using administrative data. An individual was identified as T2DM if the individual had: ≥ 2 medical claims for T2DM coded 250.xx excluding type 1 diabetes; or ≥ 2 pharmacy claims related to T2DM; or ≥ 2 combined medical claims, pharmacy claims for T2DM in 12 months. A T2DM individual was in “remission” if they had no T2DM related claims for more than 12 months continuously. This is different from the standard American Diabetes Association (ADA) definition of remission which includes HbA1c values and hence is represented in quotation (as “remission”). 10,059 T2DM individuals were evaluated over a period of 8 years from 2008 to 2015. Cox proportional hazards was used to identify significant variables associated with T2DM “remission.” Results: 4.97% of patients studied met the definition of T2DM “remission” in the study cohort. After adjusting for covariates this study found a number of variables associated with T2DM “remission” that were not previously reported: no statin use; low diabetes complications severity index score; no hypertension; no neuropathy; no retinopathy; race (non-white and non-African American); presence of other chronic ischemic heart disease (IHD) and females ( p < 0.05). Conclusion: T2DM “remission” in Medicare patients 65 years and older is observed in a community setting in a small proportion of non-bariatric patients.

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“…Besides, some screened hub genes were common, like CNN1 , an actin filament-associated regulatory protein expressed in smooth muscle and many types of non-muscle cells(Liu and Jin, 2016 ), and CCDC 34 , involved in bladder carcinoma pathogenesis (Gong et al, 2015 ) and non-small-cell lung cancer (Petroziello et al, 2004 ). Nevertheless, we found some other different hub genes, e.g., SLC20A1 , involved in vascular smooth muscle cell calcification (Wu et al, 2016 ) and calcific aortic valve disease (El Husseini et al, 2013 ); MAD2L2 , a component of the mitotic spindle assembly checkpoint and a crucial contributor to the control of DNA repair activity (Boersma et al, 2015 ); UBE2T , a ubiquitin-conjugating enzyme (E2) essential for Fanconi anemia and prostate cancer (Machida et al, 2006 ; Wen et al, 2015 ); SLMAP , associated with Brugada syndrome and diabetes (Ishikawa et al, 2012 ; Upadhyay et al, 2015 ); GALK1 , a major enzyme for the metabolism of galactose (Sangiuolo et al, 2004 ); GINS2 , a complex essential in the initiation of DNA replication and progression of DNA replication fork (Liang et al, 2016 ). Additionally, role for FAM198B in AAD is hitherto unknown.…”

Section: Discussionmentioning

confidence: 99%

Weighted Gene Co-expression Network Analysis Identifies FKBP11 as a Key Regulator in Acute Aortic Dissection through a NF-kB Dependent Pathway

Wang

Liu

et al. 2017

Front. Physiol.

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Acute aortic dissection (AAD) is a life-threatening disease. Despite the higher risk of mortality, currently there are no effective therapies that can ameliorate AAD development or progression. Identification of meaningful clusters of co-expressed genes or representative biomarkers for AAD may help to identify new pathomechanisms and foster development of new therapies. To this end, we performed a weighted gene co-expression network analysis (WGCNA) and calculated module-trait correlations based on a public microarray dataset (GSE 52093) and discovered 9 modules were found to be related to AAD. The module which has the strongest positive correlation with AAD was further analyzed and the top 10 hub genes SLC20A1, GINS2, CNN1, FAM198B, MAD2L2, UBE2T, FKBP11, SLMAP, CCDC34, and GALK1 were identified. Furthermore, we validated the data by qRT-PCR in an independent sample set originated from our study center. Overall, the qRT-PCR results were consistent with the results of the microarray analysis. Intriguingly, the highest change was found for FKBP11, a protein belongs to the FKBP family of peptidyl-prolyl cis/trans isomerases, which catalyze the folding of proline-containing polypeptides. In congruent with the gene expression analysis, FKBP11 expression was induced in cultured endothelial cells by angiotensin II treatment and endothelium of the dissected aorta. More importantly we show that FKBP11 provokes inflammation in endothelial cells by interacting with NF-kB p65 subunit, resulting in pro-inflammatory cytokines production. Accordingly, siRNA mediated knockdown of FKBP11 in cultured endothelial cells suppressed angiotensin II induced monocyte transmigration through the endothelial monolayer. Based on these data, we hypothesize that pro-inflammatory cytokines elicited by FKBP11 overexpression in the endothelium under AAD condition could facilitate transendothelial migration of the circulating monocytes into the aorta, where they differentiate into active macrophages and secrete MMPs and other extracellular matrix (ECM) degrading proteins, contributing to sustained inflammation and AAD. Taken together, our data identify important role of FKBP11 which can serve as biomarker and/or therapeutic target for AAD.

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Role of SLMAP genetic variants in susceptibility of diabetes and diabetic retinopathy in Qatari population

Cited by 14 publications

References 38 publications

Statins are associated with new onset type 2 diabetes mellitus (T2DM) in Medicare patients ≥65 years

Statins are associated with new onset type 2 diabetes mellitus (T2DM) in Medicare patients ≥65 years

Type 2 Diabetes Mellitus (T2DM) “Remission” in Non-bariatric Patients 65 Years and Older

Weighted Gene Co-expression Network Analysis Identifies FKBP11 as a Key Regulator in Acute Aortic Dissection through a NF-kB Dependent Pathway

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