Plasma levels of MASP-1, MASP-3 and MAp44 in patients with type 2 diabetes: influence of glycaemic control, body composition and polymorphisms in the <i>MASP1</i> gene

Krogh, Sara; Holt, Charlotte B.; Steffensen, Rudi; Funck, Kristian Løkke; Høyem, Pernille; Laugesen, Esben; Poulsen, Per Løgstrup; Thiel, Steffen; Hansen, Troels Krarup

doi:10.1111/cei.12963

Cited by 14 publications

(22 citation statements)

References 32 publications

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“…However, none of the observed genotype-dependent differences reached statistical significance, probably due to the sample size and the proportion of GG-genotype in our population. Nevertheless, the association of rs3774275 with the MASP1 serum concentration has also been documented in other studies ( 38 , 60 ), where a GG-genotype has been linked with an increased amount of MASP1, ranging between 11 and 13% over the other genotypes. In our population, we observed a similar increase in the GG-genotype of the healthy study group.…”

Section: Resultssupporting

confidence: 60%

“…The SNP rs3774275 is located in the mutually exclusive splicing region in intron 8 of the MASP-1/3 gene and is responsible for the alternative splicing and the regulation of serum levels of MASP1 protein and its splice variants MASP3 and MAp44 ( 38 ). Two independent studies by Ammitzboll et al and Krogh et al recently showed that rs3774275 is associated with MASP1 serum concentrations ( 38 , 60 ). In both studies, they observed that the G allele was related to higher MASP1 levels ( 38 , 60 ).…”

Section: Discussionmentioning

confidence: 99%

“…Two independent studies by Ammitzboll et al and Krogh et al recently showed that rs3774275 is associated with MASP1 serum concentrations ( 38 , 60 ). In both studies, they observed that the G allele was related to higher MASP1 levels ( 38 , 60 ). In our study, we also observed higher MASP1 levels in the GG-genotype of the control population, but failed to reach statistical significance, probably due to the small sample size for this minor genotype.…”

Section: Discussionmentioning

confidence: 99%

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AmpliSeq Screening of Genes Encoding the C-Type Lectin Receptors and Their Signaling Components Reveals a Common Variant in MASP1 Associated with Pulmonary Tuberculosis in an Indian Population

et al. 2018

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Tuberculosis (TB) is a multifactorial disease governed by bacterial, host and environmental factors. On the host side, growing evidence shows the crucial role that genetic variants play in the susceptibility to Mycobacterium tuberculosis (Mtb) infection. Such polymorphisms have been described in genes encoding for different cytokines and pattern recognition receptors (PRR), including numerous Toll-like receptors (TLRs). In recent years, several members of the C-type lectin receptors (CTLRs) have been identified as key PRRs in TB pathogenesis. Nevertheless, studies to date have only addressed particular genetic polymorphisms in these receptors or their related pathways in relation with TB. In the present study, we screened the main CTLR gene clusters as well as CTLR pathway-related genes for genetic variation associated with pulmonary tuberculosis (PTB). This case-control study comprised 144 newly diagnosed pulmonary TB patients and 181 healthy controls recruited at the Bhagwan Mahavir Medical Research Center (BMMRC), Hyderabad, India. A two-stage study was employed in which an explorative AmpliSeq-based screening was followed by a validation phase using iPLEX MassARRAY. Our results revealed one SNP (rs3774275) in MASP1 significantly associated with PTB in our population (joint analysis p = 0.0028). Furthermore, serum levels of MASP1 were significantly elevated in TB patients when compared to healthy controls. Moreover, in the present study we could observe an impact of increased MASP1 levels on the lectin pathway complement activity in vitro. In conclusion, our results demonstrate a significant association of MASP1 polymorphism rs3774275 and MASP1 serum levels with the development of pulmonary TB. The present work contributes to our understanding of host-Mtb interaction and reinforces the critical significance of mannose-binding lectin and the lectin-complement pathway in Mtb pathogenesis. Moreover, it proposes a MASP1 polymorphism as a potential genetic marker for TB resistance.

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Section: Resultssupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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AmpliSeq Screening of Genes Encoding the C-Type Lectin Receptors and Their Signaling Components Reveals a Common Variant in MASP1 Associated with Pulmonary Tuberculosis in an Indian Population

et al. 2018

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“…However, some limitations should be considered. Two women with pre‐eclampsia had gestational diabetes mellitus, which could influence lectin pathway protein serum concentrations, as described for non‐pregnant diabetic subjects . However, since this was a low proportion of the entire cohort, we assumed that it would not influence our results.…”

Section: Discussionsupporting

confidence: 58%

Lectin pathway proteins of the complement system in normotensive pregnancy and pre‐eclampsia

Larsen

Andersen

Hvas

et al. 2019

American J Rep Immunol

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Problem:The lectin pathway of the complement system may be involved in the pathogenesis of pre-eclampsia. We aimed to investigate changes in serum concentrations of a broad range of lectin pathway proteins during normal pregnancy and their association with pre-eclampsia, placental infarctions and intrauterine growth restriction (IUGR). Method of study:We included 51 women with normotensive pregnancies and 54 women with pregnancies complicated by pre-eclampsia. Blood samples were obtained at gestational weeks 16, 33, 37, and after delivery for the normotensive pregnant women and before and after delivery for women with pre-eclampsia. Mannose-binding lectin (MBL), H-and M-ficolin, collectin liver-1 (CL-L1), MBL-associated serine protease (MASP)-1, MASP-2 and MASP-3 and MBL-associated proteins of 19 (MAp19) and 44 (MAp44) kDa were analysed. Clinical information was obtained from medical records. The placentae were examined by two experienced perinatal pathologists.Results: Lectin pathway protein concentrations generally increased during normal pregnancy and decreased after delivery in both normotensive pregnant women and women with pre-eclampsia. Exceptions were MASP-3 which increased after delivery in both groups (P < 0.0001) and H-ficolin which increased after delivery in pre-eclampsia (P < 0.0001). H-ficolin (P < 0.0001), M-ficolin (P = 0.005) and MASP-3 (P = 0.03) concentrations were lower in women with pre-eclampsia than in normotensive pregnant women. Low MASP-3 concentrations were associated with placental infarction (P = 0.03) and IUGR (P = 0.04). Low H-ficolin concentrations were associated with IUGR (P < 0.01). Conclusion:In general, lectin pathway protein serum concentrations increased during normal pregnancy. H-ficolin and MASP-3 may be involved in the pathophysiology of pre-eclampsia and IUGR and could be potential future pre-eclampsia biomarkers. K E Y W O R D Scomplement pathway, ficolin, intrauterine growth restriction, mannose-binding lectin, mannose-binding protein-associated serine proteases, pre-eclampsia

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“…Moreover, higher MASP levels were associated with both higher fasting and 2-h-glucose levels [ 23 ]. Krogh and coworkers have recently confirmed this cross-sectional association by reporting higher MASP-1 levels in persons with type 2 diabetes compared to controls [ 31 ].…”

Section: Discussionmentioning

confidence: 89%

Protein markers and risk of type 2 diabetes and prediabetes: a targeted proteomics approach in the KORA F4/FF4 study

et al. 2018

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The objective of the present study was to identify proteins that contribute to pathophysiology and allow prediction of incident type 2 diabetes or incident prediabetes. We quantified 14 candidate proteins using targeted mass spectrometry in plasma samples of the prospective, population-based German KORA F4/FF4 study (6.5-year follow-up). 892 participants aged 42–81 years were selected using a case-cohort design, including 123 persons with incident type 2 diabetes and 255 persons with incident WHO-defined prediabetes. Prospective associations between protein levels and diabetes, prediabetes as well as continuous fasting and 2 h glucose, fasting insulin and insulin resistance were investigated using regression models adjusted for established risk factors. The best predictive panel of proteins on top of a non-invasive risk factor model or on top of HbA1c, age, and sex was selected. Mannan-binding lectin serine peptidase (MASP) levels were positively associated with both incident type 2 diabetes and prediabetes. Adiponectin was inversely associated with incident type 2 diabetes. MASP, adiponectin, apolipoprotein A-IV, apolipoprotein C-II, C-reactive protein, and glycosylphosphatidylinositol specific phospholipase D1 were associated with individual continuous outcomes. The combination of MASP, apolipoprotein E (apoE) and adiponectin improved diabetes prediction on top of both reference models, while prediabetes prediction was improved by MASP plus CRP on top of the HbA1c model. In conclusion, our mass spectrometric approach revealed a novel association of MASP with incident type 2 diabetes and incident prediabetes. In combination, MASP, adiponectin and apoE improved type 2 diabetes prediction beyond non-invasive risk factors or HbA1c, age and sex. Electronic supplementary material The online version of this article (10.1007/s10654-018-0475-8) contains supplementary material, which is available to authorized users.

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Plasma levels of MASP-1, MASP-3 and MAp44 in patients with type 2 diabetes: influence of glycaemic control, body composition and polymorphisms in the MASP1 gene

Cited by 14 publications

References 32 publications

AmpliSeq Screening of Genes Encoding the C-Type Lectin Receptors and Their Signaling Components Reveals a Common Variant in MASP1 Associated with Pulmonary Tuberculosis in an Indian Population

AmpliSeq Screening of Genes Encoding the C-Type Lectin Receptors and Their Signaling Components Reveals a Common Variant in MASP1 Associated with Pulmonary Tuberculosis in an Indian Population

Lectin pathway proteins of the complement system in normotensive pregnancy and pre‐eclampsia

Protein markers and risk of type 2 diabetes and prediabetes: a targeted proteomics approach in the KORA F4/FF4 study

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