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1.
Jeffery S Crosby A Plange-Rhule J Amoah-Danquah J Acheampong JW Eastwood JB Malik AK 《Genetic testing》1999,3(4):375-377
Mutations in the HFE gene on chromosome 6 are believed to cause the iron overload disorder hemochromatosis, the most common single gene disorder in northern Europeans. Two mutations have been described previously: C282Y, with an allele frequency of between 3% and 10% in the caucasian population, and H63D, which has an allele frequency of 16%. Published data shows that C282Y appears to be causative in the homozygous state, while the frequency of H63D/C282Y compound heterozygotes is much greater than expected in patient groups. There also appears to be a slightly elevated risk for H63D homozygotes. Hemochromatosis has been thought to be primarily a caucasian disorder. We have studied 97 healthy, black Ghanaian subjects, whose parents and grandparents were also African, to find the frequency of the two mutations. C282Y was absent, while H63D occurred in 2 individuals. These differences are significant at the 0.05 and 0.001 levels, respectively. The prevalence of H63D homozygotes in this population at 1 in 10,000 is clearly of no use in studying the effect of this genotype on phenotype. However, this study suggests an absence of the C282Y mutation in African populations, and the possibility that other populations might provide different genotypes and hence an analysis of H63D risk. A possible heterozygote advantage for the mutation is discussed. 相似文献
2.
Reelin is an extracellular signaling protein that plays an important role in the development of the central nervous system. Post-mortem studies have shown lower reelin protein levels in the brains of patients with schizophrenia and bipolar disorder compared with controls. Genetic studies have also shown that mutations in the reelin gene (RELN) increase the risk for schizophrenia and bipolar disorder. We evaluated whether an RELN gene variant, rs362719, which has been associated with increased susceptibility to bipolar disorder, is also associated with susceptibility to schizophrenia. We included 405 Chinese Han schizophrenia patients and 390 controls in our study. The polymorphism was genotyped by PCR and RFLP methods. We found a significant difference in allele frequency distribution (P< 0.05) between schizophrenia patients and controls. The frequency of the A allele was significantly higher in schizophrenia patients than in healthy controls. The effect of SNP rs362719 on allele distribution was significant in female (P < 0.05) but not in male participants (P = 0.473). Besides the gender factor, demographic and clinical characteristics of the rs362719 genotype groups were also analyzed using the chi-square test, but no significant differences were found. We conclude that rs362719 of the RELN gene is associated with susceptibility to schizophrenia in Chinese Han, possibly through a gender-specific mechanism. Further studies will be needed to confirm this genetic risk factor for schizophrenia. 相似文献
3.
Disrupted in schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder 总被引:17,自引:0,他引:17
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Hodgkinson CA Goldman D Jaeger J Persaud S Kane JM Lipsky RH Malhotra AK 《American journal of human genetics》2004,75(5):862-872
Schizophrenia, schizoaffective disorder, and bipolar disorder are common psychiatric disorders with high heritabilities and variable phenotypes. The Disrupted in Schizophrenia 1 (DISC1) gene, on chromosome 1q42, was originally discovered and linked to schizophrenia in a Scottish kindred carrying a balanced translocation that disrupts DISC1 and DISC2. More recently, DISC1 was linked to schizophrenia, broadly defined, in the general Finnish population, through the undertransmission to affected women of a common haplotype from the region of intron 1/exon 2. We present data from a case-control study of a North American white population, confirming the underrepresentation of a common haplotype of the intron 1/exon 2 region in individuals with schizoaffective disorder. Multiple haplotypes contained within four haplotype blocks extending between exon 1 and exon 9 are associated with schizophrenia, schizoaffective disorder, and bipolar disorder. We also find overrepresentation of the exon 9 missense allele Phe607 in schizoaffective disorder. These data support the idea that these apparently distinct disorders have at least a partially convergent etiology and that variation at the DISC1 locus predisposes individuals to a variety of psychiatric disorders. 相似文献
4.
Genetic epidemiology studies of hereditary hemochromatosis (HHC) have shown a high prevalence of the C282Y mutation in individuals of the North Western European origin, whereas lower prevalence of HFE gene mutations was detected in the populations from southern European countries. However, no HFE mutation prevalence data have been provided for the population of Bosnia-Herzegovina so far. Therefore, the aim of this study was to determine the frequency of the C282Y and H63D HFE gene mutations in the population of Bosnia-Herzegovina. Among 200 analysed subjects 8 (4%) were C282Y heterozygotes; no C282Y homozygotes were found. The frequency of the H63D allele was 11.5%. There were 33 (16.5%) heterozygotes and 6 (3%) homozygotes for the H63D mutation. One (0.5%) compound heterozygote C282Y/H63D was identified. The observed C282Y and H63D allele frequency was 2.25% (95% confidence interval: 1.2-4.2) and 11.5% (95% confidence interval: 8.7-14.9), respectively. The prevalence of the C282Y and H63D mutations was estimated in Bosnia-Herzegovina, which fit well in the European northwest-to-southeast gradient of the C282Y mutation distribution. In addition, these results have an important implication for clinical evaluation of HHC in Bosnia-Herzegovina. 相似文献
5.
Hereditary hemochromatosis (HH) is one of the most common autosomal recessive disorders of iron metabolism among Caucasians, and it is associated with C282Y mutation of the HFE gene in populations of Celtic origins. A second mutation, H63D, shows a very high widespread frequency, although its role in iron metabolism is still inconclusive. There are no data on the frequencies of these two mutations in Sardinia, an island in the Mediterranean sea that has not been invaded by Celtic peoples. We examined 836 chromosomes from Sardinian subjects and tested for the mutation by restriction enzyme digestion of PCR products. Among the 836 analyzed chromosomes, we found a C282Y allele frequency of 0.0036 and an H63D allele frequency of 0.173. These data could explain the observed rarity of HH in Sardinia. The high allele frequency of H63D and the rarity of HH in Sardinia is suggestive that this mutation is not a major contributor to this disease. 相似文献
6.
Familial Mediterranean fever (FMF) is a genetic disorder with acute inflammatory serosal attacks due to MEFV gene mutations
which resides in chromosome 16. Lack of a C5a inhibitor activity in the peritoneum has previously been proposed in part to
contribute in propagation of the serosal inflammation in FMF attacks. The aim of this study is to investigate C5a receptor
(C5aR) gene polymorphism in patients with FMF and its relation to the main features of the disease. A polymorphism in the
coding region of C5aR gene leading to C to T transition at nucleotide position 450 has been investigated in 85 non-related
Turkish FMF patients and 160 non-related healthy controls by using PCR-RFLP. The frequencies of C5aR gene 450 CT genotype
and T allele were not significantly different between Turkish FMF patients and healthy subjects (14.12 and 8.24% for FMF vs.
10 and 5% for controls, respectively). C5aR gene 450 CT genotype tended to associate with the presence Henoch-Schonlein purpura
(OR: 1.25, 95% CI: 0.917–1.704, P = 0.017) but with no other clinical findings of the disease. C5aR polymorphism might be searched in populations having high
prevalence of FMF. 相似文献
7.
Mikhaĭlova SV Kobzev VF Kulikov IV Romashchenko AG Khasnulin VI Voevoda MI 《Genetika》2003,39(7):988-995
Expression of hereditary hemochromatosis as well as predisposition to iron overload syndrome and sporadic porphyria cutanea tarda are currently believed to be associated with the inheritance of certain allelic variants of the HFE gene. Allele frequencies of the C282Y (845A) and H63D (187G) mutations in the HFE gene in human populations of different races are remarkably different, and the prevalence of the S65C (193T) mutation is still poorly studied. In the present study we estimated allele frequencies of HFE mutations in Russians and in a number of Siberian ethnic indigenous populations. In Russians, allele frequencies of the C282Y, H63D and S65C mutations were 3.7, 13.3 and 1.7%, respectively. These values were similar to those observed in populations of Europe. The C282Y mutation was not detected in the population samples of Siberian ethnic groups, including Mansis, Khantys (Finno-Ugric group), Altaians, and Nivkhs (Mongoloids), suggesting that the frequency of this allele in the populations examined was lower than 1%. The frequency of the C282Y allele in the Tuvinian and Chukchi samples (Mongoloids) constituted 0.45 and 0.8%, respectively. Furthermore, pedigree analysis of both Chukchi carriers discovered showed that some of their ancestors were from other ethnic groups. Low frequencies of this allelic variant is typical of many Eastern Asian populations, which are also characterized by rather low frequencies of the H63D variant. In contrast, in some ethnic groups of Western Siberia allelic frequency of the H63D mutation is rather high, constituting 8.7% in Altaians, 15.5% in Mansis, and 11.3% in Khantys. The frequency of this allele in Tuvinians, Nivkhs, and Chukchis constituted 5, 4.7, and 0.8%, respectively. These findings make it possible to estimate the proportion of individuals predisposed to iron overload syndrome in different Russian ethnic groups. The HFE allele frequency distribution patterns observed in the populations examined pointed to pre-Celtic appearance of the CY82 allele. It also provides elucidation of the evolutionary genetic relationships between Siberian ethnic groups and the contemporary populations of Eastern and Western Europe. 相似文献
8.
One of the world highest prevalence estimates of myotonic dystrophy (DM) has been reported in the Croatian region Istria. To analyse the population genetic characteristics of DM locus in Istria, two intragenic and three extragenic polymorphic markers were tested. The Southern blot technique was used for D19S63 locus analysis, whereas PCR analysis was performed for CKMM, Alu polymorphism, DMPK (G/T) intron 9/HinfI polymorphism, and D19S207 genetic markers. The compound haplotypes segregating with DM were established. A complete association between the DM mutation and D19S63, D19S207, intron 9/HinfI polymorphism and Alu polymorphism markers were found. In all DM chromosomes: D19S63 and Alu markers had the allele 1 in common; D19S207 had the allele 3 in common, DMPK (G/T) intron 9/HinfI marker had the allele 2 in common. The analysis of CKMM polymorphism revealed genotype heterogeneity; in DM chromosomes either allele 2 or allele 4 were found. The haplotype analysis in the population of Croatian Istria supports the linkage disequilibrium between the DM mutation and Alu polymorphism, intron 9/HinfI polymorphism, D19S63 and D19S207 markers as reported worldwide. The results of the haplotype analysis suggest a common origin of the mutation in Istrian population. 相似文献
9.
Marianna Trebunova Eva Slaba Viera Habalova Zuzana Gdovinova 《Central European Journal of Biology》2008,3(1):49-54
Angiotensin-converting enzyme (ACE) has been reported to show altered activity in patients with neurological diseases. The
recent studies found that a 287 bp insertion/deletion (I/D) polymorphism of the ACE gene may be associated with susceptibility
to Alzheimer’s disease (AD) but the results have been heterogenous between studies in Europe. In the present study we examined
for the first time the association of ACE I/D polymorphism along with APOE genotype in 70 sporadic AD and 126 control subjects
in Slovak Caucasians (Central Europe). An increased risk for AD was observed in subjects with at least one APOE*E4 allele
(OR=3.99, 95% CI=1.97–8.08). No significant differences for the genotype distribution or the allele frequency were revealed
comparing controls and patients for ACE gene. Gene-gene interaction analysis showed increase of the risk to develop AD in
subjects carrying both the ACE DD genotype and the APOE*E4 allele (OR=10.32, 95% C.I. 2.67–39.81). 相似文献
10.
Libia M Rodriguez Mabel C Giraldo Laura I Velasquez Cristiam M Alvarez Luis F Garcia Marlene Jimenez-Del-Rio Carlos Velez-Pardo 《Genetics and molecular biology》2015,38(1):8-13
A significant association between HFE gene mutations and the HLA-A*03-B*07 and
HLA-A*29-B*44 haplotypes has been reported in the Spanish population. It has been
proposed that these mutations are probably connected with Celtic and North African
ancestry, respectively. We aimed to find the possible ancestral association between
HLA alleles and haplotypes associated with the HFE gene (C282Y and
H63D) mutations in 214 subjects from Antioquia, Colombia. These were 18 individuals
with presumed hereditary hemochromatosis (“HH”) and 196 controls. The HLA-B*07 allele
was in linkage disequilibrium (LD) with C282Y, while HLA-A*23, A*29, HLA-B*44, and
B*49 were in LD with H63D. Altogether, our results show that, although the H63D
mutation is more common in the Antioquia population, it is not associated with any
particular HLA haplotype, whereas the C282Y mutation is associated with
HLA-A*03-B*07, this supporting a northern Spaniard ancestry. 相似文献
11.
12.
Ikeda M Ozaki N Suzuki T Kitajima T Yamanouchi Y Kinoshita Y Kishi T Sekine Y Iyo M Harano M Komiyama T Yamada M Sora I Ujike H Inada T Iwata N 《Genes, Brain & Behavior》2007,6(1):107-112
Recent investigations suggest that the AKT/glycogen synthase kinase 3 (GSK3) signaling cascade may be associated with the pathophysiology of schizophrenia and methamphetamine (METH) use disorder. One important molecule related to this cascade is beta-arrestin 2 (ARRB2). We therefore conducted a genetic case-control association analysis of the gene for ARRB2 with schizophrenia and METH use disorder in a Japanese population (547 people with schizophrenia, 177 with METH use disorder and 546 controls). A possible association of 'tag single nucleotide polymorphisms (SNPs)' was found in METH use disorder (rs1045280: P(genotype) = 0.0118, P(allele) = 0.00351; rs2036657: P(allele) = 0.0431; rs4790694: P(genotype) = 0.0167, P(allele) = 0.0202), but no association was found with schizophrenia. We also evaluated the gene-gene interactions among ARRB2, AKT1, and GSK3B, which we previously reported for each of these diseases. However, no interaction was seen in our samples. This is the first association analysis of ARRB2, and our results indicate that ARRB2 may play a role in the pathophysiology of METH use disorder. 相似文献
13.
14.
Nadalin S Rubesa G Giacometti J Vulin M Tomljanović D Vraneković J Kapović M Buretić-Tomljanović A 《Prostaglandins, leukotrienes, and essential fatty acids》2008,78(6):351-360
The enzymes phospholipases A2 are believed to be involved in the pathology of schizophrenia. We investigated allelic and genotype frequencies of PLA2G4A BanI polymorphism and the rs4375 in PLA2G6A in Croatian schizophrenic patients (n=81) and controls (n=182), using PCR/RFLP. Genotype and allelic frequencies of both loci, alone or in combination did not show significant difference (chi2-test). Allele-wise and genotype-wise meta-analyses of BanI polymorphism in case-control and family-based studies also revealed no significant association with schizophrenia. Multiple logistic regression analyses revealed statistically significant association between several items from PANSS general psychopathology scale and BanI polymorphism in PLA2G4A. BanI polymorphism further showed a significant impact on mean age of the onset of disease in males (betaA1=0.351, P=0.021; Spearman's rA1=0.391, P=0.010) indicating lower mean age at admission in homozygous A2A2 males. 相似文献
15.
Funke BH Lencz T Finn CT DeRosse P Poznik GD Plocik AM Kane J Rogus J Malhotra AK Kucherlapati R 《Molecular medicine (Cambridge, Mass.)》2007,13(7-8):407-414
A significant portion of patients with 22q11 deletion syndrome (22q11DS) develop psychiatric disorders, including schizophrenia and other psychotic and affective symptoms, and the responsible gene/s are assumed to also play a significant role in the etiology of nonsyndromic psychiatric disease. The most common psychiatric diagnosis among patients with 22q11DS is schizophrenia, thought to result from neurotransmitter imbalances and also from disturbed brain development. Several genes in the 22q11 region with known or suspected roles in neurotransmitter metabolism have been analyzed in patients with isolated schizophrenia; however, their contribution to the disease remains controversial. Haploinsufficiency of the TBX1 gene has been shown to be sufficient to cause the core physical malformations associated with 22q11DS in mice and humans and via abnormal brain development could contribute to 22q11DS-related and isolated psychiatric disease. 22q11DS populations also have increased rates of psychiatric conditions other than schizophrenia, including mood disorders. We therefore analyzed variations at the TBX1 locus in a cohort of 446 white patients with psychiatric disorders relevant to 22q11DS and 436 ethnically matched controls. The main diagnoses included schizophrenia (n = 226), schizoaffective disorder (n = 67), bipolar disorder (n = 82), and major depressive disorder (n = 29). We genotyped nine tag SNPs in this sample but did not observe significant differences in allele or haplotype frequencies in any of the analyzed groups (all affected, schizophrenia and schizoaffective disorder, schizophrenia alone, and bipolar disorder and major depressive disorder) compared with the control group. Based on these results we conclude that TBX1 variation does not make a strong contribution to the genetic etiology of nonsyndromic forms of psychiatric disorders commonly seen in patients with 22q11DS. 相似文献
16.
Background
Hepatocellular carcinoma (HCC) associated to infection with hepatitis C virus (HCV) has become the fastest-rising cause of cancer-related deaths. Genetic variations may play an important role in the development of HCC in HCV patients. Ghrelin exerts anti-inflammatory, antifibrotic and hepatoprotective effects on chronically injured hepatic tissues. Ghrelin gene shows several single nucleotide polymorphisms (SNPs) including − 604G/A, Arg51Gln, and Leu72Met. Hemochromatosis gene (HFE) mutations namely C282Y and H63D may cause hepatic iron overload, thus increasing the risk of HCC in HCV patients.Aim
To investigate the association of progression of HCC with ghrelin and HFE gene polymorphisms in HCV Egyptian patients.Methods
Seventy-nine chronic HCV patients (thirty-nine developed HCC and forty did not), and forty healthy control subjects were included in the study. The polymorphisms were evaluated by PCR/RFLP analysis, and related protein levels were measured by either ELISA or colorimetric assays.Results
The three tested SNPs on ghrelin gene were detected in the studied groups, only one SNP (Arg51Gln) showed significantly higher GA, AA genotypes and A allele frequencies in hepatitis C patients who developed HCC than in hepatitis C patients without HCC and controls. Of the two mutations studied on HFE gene only H63D heterozygous allele was detected, and its frequency did not statistically differ among studied groups.Conclusion
Our results suggest that A allele at position 346 of the ghrelin gene is associated with susceptibility to HCC in hepatitis C patients. 相似文献17.
Pereira AC Mota GF Krieger JE 《Human biology; an international record of research》2001,73(1):145-151
Genetic testing for hemochromatosis may have important implications for diagnosis and screening of the disease. However, the relative importance of mutations in the gene for hereditary hemochromatosis, HFE, may vary among populations, when the mutant allele frequencies and their penetrance in a particular genetic and environmental background are taken into account. We present data on the allele and genotype frequencies and population structure of two HFE genetic variants in three different ethnic groups from a highly mixed urban population (S?o Paulo, Brazil). Allele frequencies for both the C282Y and H63D HFE mutations showed significant differences among the studied populations (for the C282Y mutation, Euro-Brazilian 3.7%, admixed 0.7%, Afro-Brazilian 0.5%; and for the H63D mutation, Euro-Brazilian 20.3%, admixed 13.0%, Afro-Brazilian 6.4). The data substantiate a European origin for these mutations. Furthermore, they provide a basis for a more rational strategic planning of population screening programs for the disease. 相似文献
18.
Partial biotinidase deficiency is usually due to the D444H mutation in the biotinidase gene 总被引:1,自引:0,他引:1
Katie L. Swango Mübeccel Demirkol Gülden Hüner E. Pronicka Jolanta Sykut-Cegielska Andreas Schulze B. Wolf 《Human genetics》1998,102(5):571-575
Newborn screening for biotinidase deficiency has identified children with profound biotinidase deficiency (<10% of mean normal
serum activity) and those with partial biotinidase deficiency (10%–30% of mean normal serum activity). Children with partial
biotinidase deficiency and who are not treated with biotin do not usually exhibit symptoms unless they are stressed (i.e.,
prolonged infection). We found that 18 of 19 randomly selected individuals with partial deficiency have the transversion missense
mutation G1330>C, which substitutes a histidine for aspartic acid444 (D444H) in one allele of the biotinidase gene. We have
previously estimated that the D444H mutation results in 48% of normal enzyme activity for that allele and occurs with an estimated
frequency of 0.039 in the general population. The D444H mutation in biotinidase deficiency is similar to the Duarte variant
in galactosemia. The D444H mutation in one allele in combination with a mutation for profound deficiency in the other allele
is the common cause of partial biotinidase deficiency.
Received: 8 December 1997 / Accepted: 22 January 1998 相似文献
19.
The risk of new‐onset cancer associated with HFE C282Y and H63D mutations: evidence from 87,028 participants
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Yang‐Fan Lv Xian Chang Rui‐Xi Hua Guang‐Ning Yan Gang Meng Xiao‐Yu Liao Xi Zhang Qiao‐Nan Guo 《Journal of cellular and molecular medicine》2016,20(7):1219-1233
To investigate the association between mutation of HFE (the principal pathogenic gene in hereditary haemochromatosis) and risk of cancer, we conducted a meta‐analysis of all available case–control or cohort studies relating to two missense mutations, C282Y and H63D mutations. Eligible studies were identified by searching databases including PubMed, Embase and the ISI Web of Knowledge. Overall and subgroup analyses were performed and odds ratios (ORs) combined with 95% confidence intervals (CIs) were applied to evaluate the association between C282Y mutation, H63D mutation and cancer risk. Sensitivity and cumulative analyses were used to evaluate the stability of the results. A total of 36 eligible studies were included, comprising 13,680 cases and 73,348 controls. C282Y was significantly associated with elevated cancer risk in a recessive genetic model (OR: 1.991, 95% CI: 1.448–2.737). On subgroup analysis stratified by cancer type, statistically significantly increased cancer risks were found for breast cancer, colorectal cancer and hepatocellular carcinoma in a recessive model. When stratified by territory, a significantly increased risk of cancer was found in Oceanic populations in a recessive model and in Asian populations in an allele model and dominant model. H63D mutation did not significantly increase overall cancer risk in any genetic model. However, when, stratified by territory, an increased cancer risk was found in the Asian population in an allele and dominant. C282Y but not H63D mutation was related to elevated cancer risk. Further large‐scale studies considering gene–environment interactions and functional research should be conducted to further investigate this association. 相似文献
20.
Jing Zhang Ga Liao Chang Liu Lei Sun Yanyou Liu Yuhui Wang Zhou Jiang Zhengrong Wang 《Molecular biology reports》2011,38(1):349-354
Many reports have shown that the biologic rhythm could be altered due to mutations of circadian gene hClock or hPeriod, and
the mutations of circadian genes have some relationship with psychosis according to recent studies. A preliminary study has
been conducted to examine wether the T3111C single nucleotide polymorphism of the hClock gene or the length polymorphism of
the hPer3 gene is associated with the development of schizophrenia. The samples from schizophrenics (n = 148, male: 57.4%, female: 42.6%) and normal controls (n = 199, male: 59.3%, female: 40.7%) were examined. Allele frequencies of T3111C SNP of hClock were significantly different
between schizophrenics and controls (χ2 = 19.738, P < 0.05). Schizophrenics had a significantly higher frequency of the C allele compared with controls (OR = 2.613, 95% CI = 1.693–4.034).
On the other hand, there is no significant difference of allele frequencies of 18 exon of hper3 between schizophrenics and controls (χ2 = 0.192, P > 0.05). Our results suggest that the T3111C (RS1801260) polymorphism of hClock gene is associated with schizophrenia, but
it seems that the length polymorphism of 18 exon of hPer3 may not be associated with schizophrenia. It is important to address
of the relationship between circadian gene polymorphisms and dopamine functions in further study. 相似文献