The Experts below are selected from a list of 35409 Experts worldwide ranked by ideXlab platform
Deborah P Merke - One of the best experts on this subject based on the ideXlab platform.
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Complement Component 4 variations may influence psychopathology risk in patients with congenital adrenal hyperplasia due to 21 hydroxylase deficiency
Human Genetics, 2018Co-Authors: Qizong Lao, Marcia Des Jardin, Rahul Jayakrishnan, Monique Ernst, Deborah P MerkeAbstract:CYP21A2 defects result in congenital adrenal hyperplasia (CAH), an autosomal recessive disorder characterized by impaired adrenal steroidogenesis. CYP21A2 lies within the major histocompatibility complex in an area of the genome highly susceptible to genetic variation. Alterations in the neighboring Complement Component 4 isotypes C4A and C4B have been associated with psychiatric and autoimmune disease. The purpose of this study was to evaluate C4A and C4B in patients with CAH in relation to CYP21A2 genotype and psychiatric and autoimmune comorbidity. We determined the copy numbers of C4A and C4B in 145 patients with CAH (median age: 15.5 years, IQR: 16.8) and 108 carrier relatives (median age: 41.5 years, IQR: 12.0) and evaluated serum C4 concentrations. Comorbidity was determined by medical record review. Only 30% of subjects had the expected two copies each of the two C4 genes. C4B copy number determined total C4 copy number and serum C4 concentration, negatively correlated with carriership of a 30-kb deletion (P < 10− 5), and positively correlated with carriership of p.V281L (P < 10− 5). High C4A copy number (≥ 3) was associated with increased risk of having an externalizing psychiatric condition (relative risk: 2.67, 95% CI: 1.03–6.89, P = 0.04). No association was found between C4 copy number and autoimmune disease. Mutation-specific C4 structural variations commonly occur in patients with CAH and may have important clinical consequences, including increased risk of psychiatric morbidity. Trial registration NCT00250159 (November 7, 2005).
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Complement Component 4 copy number variation and cyp21a2 genotype associations in patients with congenital adrenal hyperplasia due to 21 hydroxylase deficiency
Human Genetics, 2012Co-Authors: Wuyan Chen, Miki Nishitani, Carol Van Ryzin, Nazli B Mcdonnell, Deborah P MerkeAbstract:Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder of cortisol biosynthesis caused by CYP21A2 mutations. An increase in gene copy number variation (CNV) exists at the CYP21A2 locus. CNV of C4, a neighboring gene that encodes Complement Component 4, is associated with autoimmune disease susceptibility. In this study, we performed comprehensive genetic analysis of the RP-C4-CYP21-TNX (RCCX) region in 127 unrelated 21-OHD patients (100 classic, 27 nonclassic). C4 copy number was determined by Southern blot. C4 CNV and serum C4 levels were evaluated in relation to CYP21A2 mutations and relevant phenotypes. We found that the most common CYP21A2 mutation associated with the nonclassic form of CAH, V281L, was associated with high C4 copy number (p = 7.13 × 10−16). Large CYP21A2 deletion, a common mutation associated with the classic form of CAH, was associated with low C4 copy number (p = 1.61 × 10−14). Monomodular RCCX with a short C4 gene, a risk factor for autoimmune disease, was significantly less frequent in CAH patients compared to population estimates (2.8 vs. 10.6 %; p = 1.08 × 10−4). In conclusion, CAH patients have increased C4 CNV, with mutation-specific associations that may be protective for autoimmune disease. The study of CYP21A2 in relation to neighboring genes provides insight into the genetics of CNV hotspots, an important determinant of human health.
Yang Liu - One of the best experts on this subject based on the ideXlab platform.
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vitamin e deficiency depressed fish growth disease resistance and the immunity and structural integrity of immune organs in grass carp ctenopharyngodon idella referring to nf κb tor and nrf2 signaling
Fish & Shellfish Immunology, 2017Co-Authors: Jiahong Pan, Lin Feng, Weidan Jiang, Shengyao Kuang, Ling Tang, Yongan Zhang, Xiaoqiu Zhou, Yang LiuAbstract:Abstract This study investigated the effects of dietary vitamin E on growth, disease resistance and the immunity and structural integrity of head kidney, spleen and skin in grass carp (Ctenopharyngodon idella). The fish were fed six diets containing graded levels of vitamin E (0, 45, 90, 135, 180 and 225 mg/kg diet) for 10 weeks. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila. The results showed that compared with optimal vitamin E supplementation, vitamin E deficiency caused depressed growth, poor survival rates and increased skin lesion morbidity in grass carp. Meanwhile, vitamin E deficiency decreased lysozyme and acid phosphatase activities, Complement Component 3 and Complement Component 4 contents in the head kidney, spleen and skin of grass carp (P
Nolan Kamitaki - One of the best experts on this subject based on the ideXlab platform.
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Complement Component 4 genes contribute sex specific vulnerability in diverse illnesses
bioRxiv, 2019Co-Authors: Nolan Kamitaki, Aswin Sekar, Robert E Handsaker, Heather De Rivera, Katherine Tooley, David L Morris, Kimberly E Taylor, Christopher W Whelan, Philip TomblesonAbstract:Many common illnesses differentially affect men and women for unknown reasons. The autoimmune diseases lupus and Sjogren9s syndrome affect nine times more women than men1,2, whereas schizophrenia affects men more frequently and severely3-5. All three illnesses have their strongest common-genetic associations in the Major Histocompatibility Complex (MHC) locus, an association that in lupus and Sjogren9s syndrome has long been thought to arise from HLA alleles6-13. Here we show that the Complement Component 4 (C4) genes in the MHC locus, recently found to increase risk for schizophrenia14, generate 7-fold variation in risk for lupus (95% CI: 5.88-8.61; p
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schizophrenia risk from complex variation of Complement Component 4
Nature, 2016Co-Authors: Nolan Kamitaki, Aswin Sekar, Heather De Rivera, Allison R Bialas, Avery Davis, Timothy R HammondAbstract:Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the Complement Component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive Complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.
Xiaoqiu Zhou - One of the best experts on this subject based on the ideXlab platform.
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vitamin e deficiency depressed fish growth disease resistance and the immunity and structural integrity of immune organs in grass carp ctenopharyngodon idella referring to nf κb tor and nrf2 signaling
Fish & Shellfish Immunology, 2017Co-Authors: Jiahong Pan, Lin Feng, Weidan Jiang, Shengyao Kuang, Ling Tang, Yongan Zhang, Xiaoqiu Zhou, Yang LiuAbstract:Abstract This study investigated the effects of dietary vitamin E on growth, disease resistance and the immunity and structural integrity of head kidney, spleen and skin in grass carp (Ctenopharyngodon idella). The fish were fed six diets containing graded levels of vitamin E (0, 45, 90, 135, 180 and 225 mg/kg diet) for 10 weeks. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila. The results showed that compared with optimal vitamin E supplementation, vitamin E deficiency caused depressed growth, poor survival rates and increased skin lesion morbidity in grass carp. Meanwhile, vitamin E deficiency decreased lysozyme and acid phosphatase activities, Complement Component 3 and Complement Component 4 contents in the head kidney, spleen and skin of grass carp (P
Wuyan Chen - One of the best experts on this subject based on the ideXlab platform.
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Complement Component 4 copy number variation and cyp21a2 genotype associations in patients with congenital adrenal hyperplasia due to 21 hydroxylase deficiency
Human Genetics, 2012Co-Authors: Wuyan Chen, Miki Nishitani, Carol Van Ryzin, Nazli B Mcdonnell, Deborah P MerkeAbstract:Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder of cortisol biosynthesis caused by CYP21A2 mutations. An increase in gene copy number variation (CNV) exists at the CYP21A2 locus. CNV of C4, a neighboring gene that encodes Complement Component 4, is associated with autoimmune disease susceptibility. In this study, we performed comprehensive genetic analysis of the RP-C4-CYP21-TNX (RCCX) region in 127 unrelated 21-OHD patients (100 classic, 27 nonclassic). C4 copy number was determined by Southern blot. C4 CNV and serum C4 levels were evaluated in relation to CYP21A2 mutations and relevant phenotypes. We found that the most common CYP21A2 mutation associated with the nonclassic form of CAH, V281L, was associated with high C4 copy number (p = 7.13 × 10−16). Large CYP21A2 deletion, a common mutation associated with the classic form of CAH, was associated with low C4 copy number (p = 1.61 × 10−14). Monomodular RCCX with a short C4 gene, a risk factor for autoimmune disease, was significantly less frequent in CAH patients compared to population estimates (2.8 vs. 10.6 %; p = 1.08 × 10−4). In conclusion, CAH patients have increased C4 CNV, with mutation-specific associations that may be protective for autoimmune disease. The study of CYP21A2 in relation to neighboring genes provides insight into the genetics of CNV hotspots, an important determinant of human health.