Abstract. Congestive heart failure, a complex disease of heterogeneous etiology, involves alterations in the expression of multiple genes. The Popeye domain-containing (POPDC) family of three novel muscle-restricted genes (POPDC1-3) is evolutionarily conserved and developmentally regulated. In mice, POPDC1 has been shown to play an important role in skeletal and cardiac muscles subjected to injury or stress. However, it has never been explored in human hearts. In biopsies from non-failing and failing human hearts, we examined the cellular distribution of POPDC1 as well as the expression patterns of POPDC1-3 mRNAs. POPDC1 was visualized by immunohistochemistry and estimated by Western immunoblotting. The mRNA levels of POPDC1-3 and ß myosin heavy chain (MYHC7) were assessed using reverse transcription/quantitative polymerase chain reaction. POPDC1 was predominantly localized in the sarcolemma with an enhanced expression in the intercalated discs. In failing hearts, many cardiomyocytes appeared deformed and POPDC1 labeling was deranged. The three POPDC mRNAs were expressed in the four heart chambers with higher transcript levels in the ventricles compared to the atria. Heart failure concurred with reduced levels of POPDC1 mRNA and protein in the left ventricle. Correlation analyses of mRNA levels among the failing heart specimens indicated the coordinated regulation of POPDC1 with POPDC3 and of POPDC2 with MYHC7. It can be concluded that POPDC gene expression is modified in end-stage heart failure in humans in a manner suggesting regulatory and/or functional differences between the three family members and that POPDC1 is particularly susceptible to this condition.

Interleukin-1beta (IL-1beta) and its endogenous antagonist IL-1 receptor antagonist (IL-1ra) play an important role in various inflammatory responses. The production of IL-1 and IL-1ra is regulated by genotypic and nongenotypic factors and is different between men and women. The aim of this study was to examine the existence of gender difference in the genetic polymorphism of these two cytokines. The genotypes of IL-1beta-511 biallelic polymorphism and that of IL-1Ra (IL-1RN) penta-allelic polymorphism were determined in 319 healthy Jewish subjects, 156 female and 163 male, using PCR amplification. The results showed that there was a gender difference in IL-1Ra gene polymorphism expressed by a higher incidence of IL1RN*1/IL1RN*1 homozygotes and a lower occurrence of IL1RN*1/IL1RN*2 heterozygotes in men compared with women. Furthermore, allele IL1RN*1 was more frequent in men, whereas allele IL1RN*2 was more prevalent in women. There was no difference in IL-1beta gene polymorphism between the two genders. It is conceivable that the gender difference in IL-1Ra gene polymorphism found in the current study may affect IL-1 and IL-1ra levels. This diversity might be one of the causes for the sex differences in immune response observed in various conditions, such as autoimmune diseases, pain perception, and premature delivery.