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Abstract: Retinol-binding protein 4 (RBP4) is a novel adipocytokine. It was observed that retinoid intoxication was related to acute attacks of gout. Furthermore, animal study has shown that colchicine inhibits RBP secretion. The aim of this study was to explore the association between RBP4 level and metabolic parameters especially uric acid in patients with type 2 diabetes mellitus. Serum RBP4 level was measured by a commercial competitive enzyme-linked immunosorbent assay kit, and its correlation with clinical and metabolic parameters was analyzed. Data on 885 subjects were used in the analysis. Pearson correlations revealed that serum RBP4 level correlated positively with age, waist circumference, waist-to-hip ratio, systolic blood pressure, total cholesterol, triglyceride, uric acid, creatinine, and urine albumin-to-creatinine ratio. Serum RBP4 level correlated negatively with estimated glomerular filtration rate but did not correlate with body mass index, homeostasis model assessment, A1C, or high-sensitivity C-reactive protein. Multiple linear regression analysis with serum RBP4 level as the dependent variable revealed that total cholesterol, triglyceride, uric acid, and albumin-to-creatinine ratio correlated independently and positively with serum RBP4 level and that estimated glomerular filtration rate correlated independently and negatively with serum RBP4 level. In conclusion, RBP4 level was independently associated with uric acid level. [Copyright &y& Elsevier]

Background: Abnormalities of collagen and elastic fibers were found in floppy mitral valves (FMV). Urokinase-plasminogen activator (PLAU) was suggested to be involved in the pathogenesis of elastin and collagen degradation in arterial aneurysm. The role of PLAU genetic variant in mitral valve prolapse (MVP) has not been studied. We, therefore, performed a case-controlled study investigating the possible relation between the PLAU gene polymorphisms and risk of MVP in Taiwan Chinese. Methods: We studied 100 patients with MVP diagnosed by echocardiography and 106 age- and sex-matched normal control subjects. The T4065C and T3995C polymorphisms of the PLAU gene were identified by polymerase chain reaction (PCR)-based restriction analysis. Results: There was a significant difference in either the genotype distribution or allelic frequencies between MVP cases and controls for PLAU gene T4065C polymorphism (P=0.0001 and 0.0002, respectively). An odds ratio for risk of MVP associated with PLAU T4065C TC genotype was 6.03 (95% confidence interval 2.11–14.83). An odds ratio for risk of MVP associated with PLAU T4065C T allele was 4.99 (95% confidence interval 1.93–12.91). There was no significant difference in either the genotype distribution or allelic frequencies between MVP cases and controls for PLAU T3995C polymorphism. Further categorization of the MVP patients into mild and severe subgroups revealed no statistical difference between these two subgroups for PLAU T4065C and T3995C polymorphisms. Conclusions: This study shows that patients with MVP have a higher frequency of PLAU T4065C TC genotype and T allele that supports a role of the PLAU T4065C polymorphism in determining the risk of MVP among the Chinese population in Taiwan. [Copyright &y& Elsevier]

Many biochemical pathways involved in hair and skin development have not been investigated. Here, we reported on the lesions and investigated the mechanism underlying hair and skin abnormalities in Zdhhc13skc4 mice with a deficiency in DHHC13, a palmitoyl-acyl transferase encoded by Zdhhc13. Homozygous affected mice showed ragged and dilapidated cuticle of the hair shaft (CUH, a hair anchoring structure), poor hair anchoring ability, and premature hair loss at early telogen phase of the hair cycle, resulting in cyclic alopecia. Furthermore, the homozygous affected mice exhibited hyperproliferation of the epidermis, disturbed cornification, fragile cornified envelope (CE, a skin barrier structure), and impaired skin barrier function. Biochemical investigations revealed that cornifelin, which contains five palmitoylation sites at cysteine residues (C58, C59, C60, C95, and C101), was a specific substrate of DHHC13 and that it was absent in the CUH and CE structures of the affected mice. Furthermore, cornifelin levels were markedly reduced when two palmitoylated cysteines were replaced with serine (C95S and C101S). Taken together, our results suggest that DHHC13 is important for hair anchoring and skin barrier function and that cornifelin deficiency contributes to cyclic alopecia and skin abnormalities in Zdhhc13skc4 mice. [ABSTRACT FROM AUTHOR]

Abstract: Xq28 duplications encompassing the methyl CpG binding protein 2 (MECP2) in males exhibit a distinct phenotype, including developmental delay, facial dysmorphism, muscular hypotonia, intellectual disability, poor or absent speech, recurrent infections and early death. The vast majority of affected males inherit the MECP2 duplication from their usually asymptomatic carrier mothers. Only a few cases with Xq28 duplication originating from de novo unbalanced X/Y translocation have been reported and the paternal origin of the aberration has only been validated in three males in the related literature. Here we present a karyotypically normal male with features characteristic of the MECP2 duplication syndrome. The genome-wide SNP genotyping shows a de novo 2.26-Mb duplication from Xq28 to the terminus. The genotypes of the SNPs within the duplicated region indicated a paternal origin. Furthermore, the results of fluorescence in situ hybridization (FISH) indicated a novel Xq:Yp translocation, characterized as der(Y)t(Y;X)(p11.32;q28), which suggests an aberrant that occurred during spermatogenesis. The phenotype is compared to the previously reported cases with Xq28 duplication originated from an unbalanced X/Y translocation, and there was no specific part of the phenotype that could be contributed to the origin of parental imbalances. This report further highlights the capacity of high-molecular cytogenetic methods, such as SNP array and FISH, in the identification of submicroscopic rearrangement, structural configuration and parental origin of aberrant while in the evaluation of children with idiopathic developmental delay and intellectual disability. [Copyright &y& Elsevier]

Background: In a previous linkage study of schizophrenia that included Taiwanese samples, the marker D22S278 (22q12.3) was significantly linked to schizophrenia (p = .001). Methods: We conducted fine mapping of the implicated genomic region, with 47 validated single nucleotide polymorphism (SNP) markers around 1 Mb of D22S278, in a Taiwanese sample of 218 pedigrees with at least 2 siblings affected with schizophrenia. We examined the association of these SNPs and their haplotypes with schizophrenia and with subgroups defined by the presence and absence of deficits in sustained attention as assessed by undegraded and degraded continuous performance tests (CPTs). We also examined subgroups defined by deficits in categories achieved in the Wisconsin Card Sort Test (WCST). Results: Three of five candidate vulnerability genes (RASD2, APOL5, MYH9, EIF3S7, and CACNG2), which had marginally significant associations with schizophrenia, had significant associations with schizophrenic patients who did not have deficits in sustained attention on the undegraded CPT (RASD2 gene SNP rs736212; p = .0008 with single locus analysis) and the degraded CPT (MYH9 gene haplotype 1-1-1-1 of SNP rs3752463 - rs1557540 - rs713839 - rs739097; p = .0059 with haplotype analysis). We also found a significant association for patients who showed no deficits in executive function as measured by categories achieved in the WCST (CACNG2 gene haplotype 2-1-1-1 of SNP rs2267360 - rs140526 - rs1883987 - rs916269; p = .0163 with haplotype analysis). Conclusions: The genes RASD2, MYH9, and CACNG2 might be vulnerability genes for neuropsychologically defined subgroups of schizophrenic patients. [Copyright &y& Elsevier]

Background: The marker D1S251 of chromosome 1q42.1 showed significant association with schizophrenia in a Taiwanese sample. We used single nucleotide polymorphism (SNP) fine mapping to search for the vulnerability genes of schizophrenia. Methods: We selected 120 SNPs covering 1 Mb around D1S251 from the public database. These selected SNPs were initially validated if allele frequency was >10%. Forty-seven validated SNPs were genotyped in 102 families with at least 2 siblings affected with schizophrenia. Results: Two SNP blocks showed significant association with schizophrenia. Block 1 (five-SNP), located between intron 2 and intron 13 of the glyceronephosphate O-acyltransferase (GNPAT) gene, showed the most significant associations using single-locus TDT (z = −2.07, p = .038, df = 1) and haplotype association analyses (z = −1.99, p = .046, df = 1). Block 2 (two-SNP), located between intron 4 and intron 5 of the disrupted-in-schizophrenia 1 (DISC1) gene, also showed the most significant results in both the single-locus (z =−3.22, p = .0013, df = 1) and haplotype association analyses (z = 3.35, p = .0008, df = 1). The association of the DISC1 gene with schizophrenia was mainly in the patient group with sustained attention deficits as assessed by the Continuous Performance Test. Conclusions: Chromosome 1q42.1 harbors GNPAT and DISC1 as candidate genes for schizophrenia, and DISC1 is associated with sustained attention deficits. [Copyright &y& Elsevier]

Background: Collagen structure is a key element in mitral valves. Collagen defects were proposed as the primary events causing floppy mitral valves (FMV). The role of collagen genetic variant in floppy mitral valve/mitral valve prolapse (FMV/MVP) has not been well studied. The purpose of this study is to investigate the possible relationship between the collagen gene polymorphisms and risk of FMV/MVP among the Chinese population in Taiwan. Methods: We studied 100 patients with FMV/MVP diagnosed by echocardiography and 243 age- and sex-matched normal control subjects. The polymorphisms of exon 31 and exon 52 of the collagen type III-α1 gene (COL3A1) were identified by polymerase chain reaction (PCR)-based restriction analysis. Results: There was a significant difference in either the genotype distribution (P<0.0001) or allelic frequencies (P<0.0001) between FMV/MVP cases and controls for COL3A1 exon 31 polymorphism. An odds ratio for risk of FMV/MVP associated with COL3A1 exon 31 GG genotype was 7.42 (95% confidence interval 4.40–12.52). An odds ratio for risk of FMV/MVP associated with COL3A1 exon 31 G allele was 2.28 (95% confidence interval 1.57–3.29). There was no significant difference in the distribution of COL3A1 exon 52 genotypes (P=0.31) and allelic frequencies (P=0.32) between FMV/MVP cases and controls. Further categorization of the FMV/MVP patients into mild and severe subgroups revealed no statistical difference from the controls for exon 31 or exon 52 polymorphism. Conclusions: This study shows that patients with FMV/MVP have higher frequency of COL3A1 exon 31 GG genotype that supports a role of the COL3A1 exon 31 polymorphism in determining the risk of FMV/MVP among the Chinese population in Taiwan. [Copyright &y& Elsevier]