Effects of MASP2 haplotypes and MASP‐2 levels in hepatitis C‐infected patients

Abstract

Mannan-binding lectin (MBL) and MBL-associated serine protease 2 (MASP-2) are components of the lectin pathway, which activate the complement system after binding to the HCV structural proteins E1 and E2. We haplotyped 11 MASP2 polymorphisms in 103 HCV patients and 205 controls and measured MASP-2 levels in 67 HCV patients and 77 controls to better understand the role of MASP-2 in hepatitis C susceptibility and disease severity according to viral genotype and fibrosis levels. The haplotype block MASP2*ARDP was associated with protection against HCV infection (OR = 0.49, p = .044) and lower MASP-2 levels in controls (p = .021), while haplotype block AGTDVRC was significantly increased in patients (OR = 7.58, p = .003). MASP-2 levels were lower in patients than in controls (p < .001) and in patients with viral genotype 1 or 4 (poor responders to treatment) than genotype 3 (p = .022) and correlated inversely with the levels of alkaline phosphatase, especially in individuals with fibrosis 3 or 4 (R = -.7, p = .005). MASP2 gene polymorphisms modulate basal gene expression, which may influence the quality of complement response against HCV. MASP-2 levels decrease during chronic disease, independently of MASP2 genotypes, most probably due to consumption and attenuation mechanisms of viral origin and by the reduced liver function, the site of MASP-2 production.

High Levels of Complement Activating Enzyme MASP-2 Are Associated With the Risk of Future Incident Venous Thromboembolism

“…Moreover, when MASP-2 was analyzed as a continuous variable, a linear association with VTE risk was noted, mainly in analyses restricted to the first 5 years of follow-up. In the pQTL analysis, we confirmed 3 previously identified genetic variants associated with plasma MASP-2 levels 44,45 and estimated that these variants explained 39% of the variance of plasma MASP-2 levels. By applying an MR approach, genetically predicted MASP-2 levels were weakly, but significantly, associated with VTE risk.…”

“…61,62 We identified 2 missense mutations in the MASP2 gene (rs12711521 and rs72550870) and 1 variant in an adjacent gene named MTOR (rs2275527). All 3 variants have previously been described, 44,45 and these gene variants explained 39% of the variation of plasma MASP-2 levels in our study. Even after excluding the variant in the adjacent gene (rs2275527), which is partly in linkage disequilibrium with one of the missense mutations in MASP2 (rs12711521), the remaining variants in the model explained an equal variation of plasma MASP-2 levels.…”

“…Although our pQTL analysis confirmed that plasma MASP-2 levels are under a strong genetic regulation, 44,45,64 the OR for VTE according to high versus low MASP-2 levels increased with shorter time between blood sampling and VTE. This implies that biological fluctuations of plasma MASP-2 during the long followup resulted in underestimation of the true associationa phenomenon called regression dilution bias.…”

Circulating complement factor H levels are associated with disease severity and relapse in autoimmune hepatitis

“… 18 , 29 Serum MASP-2 levels in patients with chronic hepatitis C (CHC) were associated with the severity of fibrosis and response to interferon treatment. 30 High C5a or C5b-9 levels in the pretreatment serum of patients with CHC were associated with a high rate of HCV RNA clearance by direct-acting antivirals. 31 In this study, we measured the serum levels of factor H, a major plasma regulator acting in the alternative pathway, in patients with AIH and analyzed their association with clinical features.…”

Polymorphisms of MASP2 gene and its relationship with mastitis and milk production in Chinese Holstein cattle

“…MASP2 levels appear to have a dual effect in HIV and HCV/HBV co-infection. Low levels of MASP2 may increase the susceptibility to infection [11,12]. MASP2 has been associated with the development risk of ischemic stroke, and the rs147270785 Ã A alleles in MASP2 can be used as a protective factor for ischemic stroke [13].…”