Polymorphisms in the Lipoprotein Lipase and Hepatic Lipase Genes and Plasma Lipid Values in the Czech Population

Summary We have determined the genotypes of two common polymorphisms in the lipoprotein lipase (S447X) and hepatic lipase (-480C/T) genes in a cohort of 285 representative selected Czech probands (131 male and 154 female), examined in 1988 and reinvestigated in 1996. The genotype distributions of both polymorphisms were in Hardy-Weinberg equilibrium and did not differ between male and female subjects. The rare allele frequency of the lipoprotein lipase polymorphism did not differ significantly from the other European populations. Compared to the German populations, the frequency of the hepatic lipase -480T allele was significantly higher in the Czech group (20% vs. 36%, p<0.0001). There were no significant associations between the lipoprotein lipase gene variants and lipid parameters measured either in 1988, or in 1996 or with changes of lipid parameters over the 8-year period. The carriers of the T-480 allele of the hepatic lipase polymorphism were found to have higher HDL cholesterol levels (p=0.02). However, this difference was confined to female subjects only. The male carriers of the -480T allele had higher concentrations of total cholesterol (p=0.03) as compared to CC-480 subjects. Both associations were observed in 1996 only. In the Slavic Czech population, a common polymorphism in the hepatic lipase gene (-480C/T), but not in the lipoprotein lipase gene (S447X), is a significant determinant of plasma HDL cholesterol in females and plasma total cholesterol in males and indicates the importance of gender-associated effects in the genetic determinations of plasma lipids

Myasthenia gravis with anti-MuSK antibodies

Myastenia gravis je autoimunitní onemocnění s tvorbou protilátek proti postsynaptické části nervosvalové ploténky. Při průkazu protilátek proti acetylcholinovým receptorům se jedná o séropozitivní myastenia gravis a pokud tyto protilátky nejsou přítomny, pak je to séronegativní myastenia gravis. U 35 % (0–49 %) séronegativních forem byla prokázána protilátka proti svalové specifické tyrozin-kináze (MuSK). Tyto anti-MuSK myasthenia gravis se vyznačují převahou postižení žen, časnějších vznikem, charakteristickým klinickým nálezem, horší a nekonstantní reakcí na léčbu inhibitory cholinesterázy. Z neurofyziologických vyšetření je důležité vyšetřit repetitivní stimulací i proximální svaly (m. trapezius, m. deltoides) a mimické svaly (m. nasalis, m. orbicularis oculi). Při vyšetření SF EMG (single-fiber EMG) je podstatně vyšší pozitivita při vyšetření m. frontalis či m. orbicularis oculi. Není indikována thymektomie. Účinná je imunoterapie – podání imunoglobulinů, plazmaferéza, kortikoidy v kombinaci s dalšími imunosupresivy. Myastenia gravis s anti-MuSK protilátkami se vyznačuje nestabilním průběhem, větší frekvencí myastenických krizí a větší terapeutickou náročností.Myasthenia gravis is an autoimmune disease with formation of antibodies against the postsynaptic part of the neuromuscular junction. When the presence of anti-acetylcholine receptor antibodies is demonstrated, the condition is referred to as seropositive myasthenia gravis; when these antibodies are absent, it is seronegative myasthenia gravis. The anti-muscle-specific tyrosine kinase (MuSK) antibody was demonstrated in 35% (0–49%) of the seronegative forms. Anti-MuSK myasthenia gravis exhibits the following features: a predominance in women, earlier onset, characteristic clinical finding, and worse and inconstant response to treatment with cholinesterase inhibitors. With regard to neurophysiological tests, it is of importance to use repetitive stimulation to examine the proximal muscles (trapezius muscle, deltoid muscle) as well as the mimic muscles (nasalis muscle, orbicularis oculi muscle). With SF EMG (single-fibre EMG), there is a substantially higher positivity in examining the frontalis muscle or the orbicularis oculi muscle. Thymectomy is not indicated. Immunotherapy is effective – the administration of immunoglobulins, plasmapheresis, and corticosteroids in combination with other immunosuppressants. Myasthenia gravis with anti-MuSK antibodies is characterized by an unstable course, a higher frequency of myasthenic crises, and greater therapeutic complexity