Acid Phosphatase Locus Research Articles

Maternal Age at Delivery and Enzyme Polymorphisms in Children with Type 1 Diabetes Mellitus

AbstractFetal genetic adaptation to environment of aging women could result in positive selection of genes that during extrauterine life increases the risk of type 1 diabetes mellitus (T1DM). We have examined the distribution of three genetic polymorphisms (acid phosphatase locus 1 [ACP1], p53 codon 72, and PTPN22) involved in T1DM risk in relation to maternal age at delivery. p53 codon 72 was determined in 281 T1DM children, ACP1 in 207 children, and PTPN22 in 216 children. Controls (blood donors) were 351 for ACP1, 271 for PTPN22, and 730 for p53 codon 72. Genotypes were determined by DNA analysis. The proportions of the three genotypes associated with T1DM are much greater in T1DM children from older mothers than in those from young mothers and in controls. The data support the hypothesis that advanced maternal age favors a positive selection of genes more adapted to the uterine environment of older women: these genes predispose to T1DM during extrauterine life.

Genetic polymorphism and natural fertility in women

Objective: To investigate the cooperative interaction among five genetic systems (phosphoglucomutase locus 1, adenosine deaminase locus 1, acid phosphatase locus 1, adenylate kinase locus 1, and haptoglobin) concerning their effects on natural fertility in humans. Natural fertility has been evaluated by a model of age related differences between the distributions of types among pregnant women. Methods: A total of 137 nonsmoking consecutive puerperaes from the white population who had delivered their first born baby in the Maternity Department of S. Massimo Hospital of Penne were studied. The phenotypes of the five systems studied were determined by starch gel electrophoresis. Statistical analysis was performed using the statistical package for the social science. Results: There was a highly significant negative correlation between maternal age and the number of genetic factors showing a lower maternal age at the birth of the first child, which suggested a positive cooperative interaction among these factors concerning their effects on fertility. Conclusions: In the relationship of mother-fetus, besides nutritional factors, genetic factors involved in immunological interaction of the embryo with the mother are of paramount importance. Haptoglobin and adenosine deaminase locus 1 polymorphisms are involved in immune reactions and our data indicate that genetic variability within these systems gives a more important contribution to variation of human fertility as compared to acid phosphatase locus 1, phosphoglucomutase locus 1 and adenylate kinase locus 1 that are mainly involved in metabolic functions.

Genetic adaptation to historical pathogen burdens

Historical pathogen burdens are examined as possible triggers for genetic adaptation. Evidence of adaptation emerges for the acid phosphatase locus 1 (ACP1), interleukin-6 (IL6), interleukin-10 (IL10 ), human leukocyte antigen (HLA) polymorphisms, along with a measure of heterozygosity over 783 alleles. Results are robust to controlling for the physical and historical environment humans faced, and to endogeneity of the historical pathogen burden measure. The present study represents a proof-of-concept which may pave the way to the analysis of future aggregate measures coming from whole-genome sequencing/genotyping data.

Association of Acid Phosphatase‐1 (ACP1) Gene Polymorphism with MAI infection.

Human acid phosphatases are normally found at low concentrations. However, pronounced changes in their synthesis occur in particular diseases, where unusually high or low enzyme expression is seen as part of the pathophysiological process. Acid Phosphatase locus 1 (ACP1) is a polymorphic enzyme controlled by a locus on chromosome 2 with three common codominant alleles: *A, *B, and *C. ACP1 shows two major isoforms, F and S. Genetic polymorphisms could contribute to natural resistance or susceptibility to the disease. Genetic screens in humans link polymorphisms in or near the ACP1 locus to a variety of inflammatory diseases including allergy and asthma. ACP1 is involved in activation, adhesion, and differentiation of T cells. Though few studies have shown the presence of ACP in human tissues, no studies have been reported linking ACP1 gene polymorphism to susceptibility to infections. In this study we investigate the role of ACP1 gene polymorphism in patients infected with Mycobacterium avium and normal healthy subjects. Mycobacterium avium complex (MAC) consists of two species: M avium and M intracellulare; because these species are difficult to differentiate, they are also collectively referred to as Mycobacterium avium‐intracellulare (MAI). Mycobacterium avium is an environmental microorganism which also exists in multiple hosts, including humans. M. avium can invade and replicate in immunocompromised hosts and also enhances permissiveness for HIV‐1 infection. DNA was extracted from blood and PCR‐RFLP method was used to detect ACP‐1 gene polymorphism. Our study showed high frequency of ACP AB haplotype (44%) in patients with infection than in individuals with no infection (24.8%) showing a significant association with infection (p<0.006). This is the first study to show an association of ACP1 gene with MAI. Our study highlights the role of gene/s polymorphism and their possible association with infection.Support or Funding InformationEisenhower Medical Center Research funds for Infectious disease.,

Hypermethylation of ACP1, BMP4, and TSPYL5 in Hepatocellular Carcinoma and Their Potential Clinical Significance

Aberrant methylation of specific genes is frequent event in hepatocellular carcinoma (HCC). Our present study aims to explore the methylation levels of acid phosphatase locus 1 (ACP1), bone morphogenetic protein 4 (BMP4), and testis-specific protein, Y-encoded-like 5 (TSPYL5) and their potential clinical applications in HCC. The methylation levels of ACP1, BMP4 and TSPYL5 were analyzed in 188 HCC tissues, 163 matched adjacent non-tumor tissues, and 29 normal liver tissues using a method of methylation-sensitive restriction enzyme-based quantitative PCR, and their associations with clinicopathological features and prognosis were evaluated. Compared with adjacent non-tumor tissues and normal liver tissues, the methylation levels of ACP1, BMP4, and TSPYL5 were significantly increased in HCC tissues (All p < 0.0001). The methylation of each individual gene could distinguish HCC tissues well from adjacent non-tumor tissues with the area under the receiver operating characteristic curves (AUC) of 0.753, 0.785 and 0.917, respectively. Furthermore, a higher methylation of BMP4 was statistically associated with worse disease-free survival (p = 0.006) and might be an independent unfavorable factor for disease-free survival by univariate and multivariate analysis (p = 0.011, HR 3.431, 95 % CI 1.333-8.833). Our findings suggest that hypermethylation of ACP1, BMP4, and TSPYL5 are common events in HCC and could be used as potentially detectable biomarkers in HCC tissues. Moreover, BMP4 could be potentially served as a methylated biomarker to predict recurrence and metastasis after hepatectomy for HCC patients. However, their potential clinical application value need to be further clarified.

The effect of genetic and non genetic factors on the association of T1D with PTPN22 genotype and with the ACP1-ADA1 joint genotype

Background: We have recently observed that the joint genotype Acid Phosphatase locus 1-Adenosine deaminase locus 1 (ACP 1 - ADA 1 ) cooperate with Phospho Tyrosine Phosphatase, non-receptor type 22 (PTPN22) in the susceptibility to Type 1 Diabetes (T1D) . Since T1D has been found associated with sex, maternal age at birth, Adenosine Deaminase locus 2 (ADA 2 ) genotype and p53 codon 72 genotype we have investigated the possible effects of these variables on the association of T1D with PTPN22 and with ACP 1 -ADA 1 joint genotype. Methods: We have reexamined the data on 314 children with T1D and on 700 controls from the White population of Rome. PTPN22, ADA 2 and p53 codon 72 genotypes were determined by DNA analysis. Statistical analysis were carried out by commercial software (SPSS). Results: The genetic and non genetic variables considered, in particular ADA 2 *2 carrier, p53 codon 72 *Pro carrier, male sex and maternal age greater than 32 years, have a positive effect on the strength of association between PTPN22 and T1D but tend to have a negative effect on the strength of association between ACP 1 -ADA 1 joint genotype and T1D. Conclusions: The results suggest that although PTPN22 and ACP 1 -ADA 1 genetic complex cooperate in the susceptibility to T1D, the mechanisms underlying the association of the two genetic systems with the disease are different.

THU0015 Association of acid phosphatase locus 1*C ALLELE with the risk of cardiovascular events in rheumatoid arthritis patients

BackgroundAcid phosphatase locus 1 (ACP1) encodes a low molecular weight phosphotyrosine phosphatase implicated in different biological functions in the cell.ObjectivesThe aim of the present study was to determine the contribution...

ACP1 Genetic Polymorphism and Coronary Artery Disease: Evidence of Effects on Clinical Parameters of Cardiac Function.

BackgroundKinases and phosphatases have an important role in the susceptibility and clinical variability of cardiac diseases. We have recently reported an association between a phosphoprotein phosphatase controlled by Acid Phosphatase locus 1 (ACP1), and Coronary artery disease (CAD) suggesting an effect on the susceptibility to this disease. In the present note we have investigated a possible role of ACP1 in the variability of clinical parameters of cardiac function.MethodsWe have studied 345 subjects admitted to Valmontone Hospital for cardiovascular diseases: 202 subjects with CAD and 143 without CAD, 53 subjects admitted to Cardiac Surgery Division of Tor Vergata University were also considered.ResultsIn diabetic patients with CAD there is a significant negative association between Left ventricular ejection fraction (LVEF) and ACP1 S isoform concentration. Genotypes with high S isoform concentration show a lower value of LVEF as compared to genotypes with low S isoform concentration. We have also found a significant positive association between cNYHA class and ACP1 S isoform. After surgical intervention, in subjects with high S isoform concentration the decrease of LVEF is more marked as compared to subjects with low S isoform concentration. Overall these observations indicate that high S isoform activity has negative effects on cardiac function. The observation in patients undergoing cardiac surgery confirms the negative association between high S isoform activity and LVEF.ConclusionsThe present study suggests that ACP1 influences both susceptibility to CAD and clinical manifestations of the disease.

Erratum to “Novel association of acid phosphatase locus 1*C allele with systemic lupus erythematosus” [Human Immunology 73 (2012) 107–110

Erratum to ‘‘Novel association of acid phosphatase locus 1 C allele with systemic lupus erythematosus’’ [Human Immunology 73 (2012) 107–110] Maria Teruel a,⇑, Jose-Ezequiel Martin , Norberto Ortego-Centeno , Juan Jimenez Alonso , Julio Sanchez-Roman , Enrique de Ramon , M. Francisca Gonzalez-Escribano , Bernardo A. Pons-Estel , Sandra D’Alfonso , Gian Domenico Sebastiani , Torsten Witte , Nunzio Bottini , Miguel A. Gonzalez-Gay , Marta E. Alarcon-Riquelme, Javier Martin a

Acid Phosphatase Locus 1 Genetic Polymorphism and Cancer Grading

BackgroundCurrently, there is a surge of interest on the possible relationship between cancer and acid phosphatase locus 1 (ACP1), an enzyme involved in the modulation of growth factors and cellular metabolism. As far as the authors know, the possible relationship between ACP1 genetic variability and cancer grading has not yet been considered. In this article, the authors have studied the relationship between ACP1 genotype and grade in colon and endometrium cancers. MethodsSeventy-one patients with colon cancer and 71 patients with endometrium cancer were studied. ACP1 genotype was determined by DNA analysis. Three-way contingency table analysis was carried out according to Sokal and Rohlf. Other statistical analyses were performed using SPSS programs. ResultsThere is a significant association between ACP1 and cancer grade mainly due to ACP1 genotypes carrying the *C allele that are much less represented in patients with low grade when compared with those with high grade. In both cancers, the concentration of S isoform is significantly lower in low grade than in high grade. The relationship between ACP1 and grade is the same in the 2 cancers. ConclusionsAssuming the presence of diverse classes of cancer, the role of ACP1 in the modulation of growth factors and cellular metabolism could have significant effects in less aggressive forms but not in more aggressive ones.

P53 codon 72 polymorphism and coronary artery disease: Evidence of interaction with ACP1

SummaryBackgroundCommon biological features between cancer and atherosclerosis suggest possible association of p53 with atherosclerotic diseases, but data on such a relationship are controversial, suggesting interactions with other variables. Acid phosphatase locus 1 (ACP1) is a polymorphic gene that controls the synthesis of an enzyme involved in important metabolic functions. Since ACP1 is associated with coronary artery disease (CAD), we searched for possible interactions between this enzyme and p53 codon 72 polymorphism with regard to their effects on susceptibility to CAD.Material/MethodsThe study included 381 patients admitted to the hospital for cardiovascular disease (232 patients with CAD and 149 with other cardiovascular problems) and 97 healthy newborns.ResultsThe proportion of subjects carrying the *Pro allele of p53 codon 72 and the high activity *B*C genotype of ACP1 is higher in CAD (10.3%) than in non-CAD patients (2.0%) and in healthy newborns (6.2%).ConclusionsThe data suggest an interaction between p53 codon 72 and ACP1 wherein a positive effect of the p53 *Pro allele on susceptibility to CAD occurs, but only in the presence of the ACP1 genotype characterized by high enzymatic activity.

Association of Genetic Markers with Mental Retardation

Five red cell genetic markers namely, acid phosphatase locus 1 (ACP1), esterase D (ESD), glyoxalase locus 1 (GLO1), superoxide dismutase (SOD) and haemoglobin (HB) and five plasma proteins namely haptoglobin (HP), ceruloplasmin (CP), group specific component (GC), transferrin (TF) and albumin (ALB) were studied in mentally retarded individuals from Visakhapatnam area of north coastal Andhra Pradesh, South India. The results were compared with the data obtained from controls. Out of studied ten genetic markers, two namely ACP1 and HP showed significant differences between patients and controls. The risk estimates were also showing a significant association.

Novel association of acid phosphatase locus 1*C allele with systemic lupus erythematosus

The red cell acid phosphatase (ACP1) gene, which encodes a low-molecular-weight phosphotyrosine phosphatase, has been suggested as a common genetic factor of autoimmunity. In the present study, we aim to investigate the possible association of ACP1 with the susceptibility of systemic lupus erythematosus (SLE). A total of 1,546 SLE patients and 1,947 healthy individuals from 4 Caucasians populations were included in the present study. Four single-nucleotide polymorphisms (SNPs) were genotyped in this study: rs10167992, rs11553742, rs7576247, and rs3828329. ACP1*A, ACP1*B, and ACP1*C codominant ACP1 alleles were determined using 2 of the SNPs and analyzed. After the meta-analysis test was performed, a significant association of rs11553742*T was observed (p(pooled) = 0.005, odds ratios = 1.37 [1.10-1.70]), retaining significance after multiple testing was applied (p(FDR) = 0.019). Our data indicate for first time the association of rs11553742*T with increased susceptibility in SLE patients.

Association of ACP1 genotypes and clinical parameters in patients with metabolic syndrome*

Acid phosphatase locus 1 (ACP1) encodes a polymorphic enzyme and has potential implications for the development of metabolic syndrome (MS) by altering insulin sensitivity. The aim of this study was to determine whether a relationship exists between ACP1 genotypes and various metabolic syndrome risk factors. Materials and methods: We employed a PCR-RFLP based genotyping of ACP1 in a cohort of 70 patients with MS and 168 healthy individuals. Results: When compared to controls, genotypes associated with low enzyme activity were observed at significantly lower frequencies in both sexes. Of note, high enzyme activity genotypes were more common in patients with MS when compared with medium and low enzyme activity genotypes. *A allele frequency was not different between patients and controls even considering sex; however, there was a good correlation of the presence of the allele with body composition, serum cortisol levels and suppressibility of cortisol, particularly in women with MS. Conclusion: Our findings suggest that low enzyme activity genotypes seem to be associated with a protective effect for the development of MS. Additionally, *A allele carriage affects body composition in women but not in men, and the presence of this allele might modulate serum cortisol levels as well as its suppressibility in both sexes, in an inverse manner.

Association between ACP1 genetic polymorphism and favism

An association between favism (a hemolytic reaction to consumption of fava beans), glucose-6-phosphate dehydrogenase deficiency (G6PD(-)) and acid phosphatase locus 1 (ACP(1)) phenotypes has been reported; the frequency of carriers of the p(a) and p(c) ACP(1) alleles was found to be significantly higher in G6PD(-) individuals showing favism than in the general population. Here, we investigated the hypothesis that favism is caused by toxic Vicia faba substances, which in some ACP(1) phenotypes cause increased phosphorylation and consequently increased glycolysis, with strong reduction in reduced glutathione production, resulting in hemolysis. It has been demonstrated that ACP(1) f isoforms have physiological functions different from those of s isoforms and are responsible for most of the phosphatase activity, in addition to being less stable in the presence of oxidizing molecules. Thus, the C, CA and A phenotypes, characterized by lower concentrations of f isoforms, could be more susceptible to damage by oxidative events compared to the other phenotypes. To test this hypothesis, the (f+s) enzymatic activity of different ACP(1) phenotypes with and without added V. faba extract was analyzed. Enzymatic activities of ACP(1) A, -CA, -C groups (low activity) and -B, -BA, -CB groups (high activity) were significantly different after addition of V. faba extract. Phenotypes A, CA and C had extremely low enzymatic activity levels, which would lead to low levels of reduced glutathione and bring about erythrocyte lysis.

Association of acid phosphatase locus 1*Callele with the risk of cardiovascular events in rheumatoid arthritis patients

IntroductionAcid phosphatase locus 1 (ACP1) encodes a low molecular weight phosphotyrosine phosphatase implicated in a number of different biological functions in the cell. The aim of this study was to determine the contribution of ACP1 polymorphisms to susceptibility to rheumatoid arthritis (RA), as well as the potential contribution of these polymorphisms to the increased risk of cardiovascular disease (CV) observed in RA patients.MethodsA set of 1,603 Spanish RA patients and 1,877 healthy controls were included in the study. Information related to the presence/absence of CV events was obtained from 1,284 of these participants. All individuals were genotyped for four ACP1 single-nucleotide polymorphisms (SNPs), rs10167992, rs11553742, rs7576247, and rs3828329, using a predesigned TaqMan SNP genotyping assay. Classical ACP1 alleles (*A, *B and *C) were imputed with SNP data.ResultsNo association between ACP1 gene polymorphisms and susceptibility to RA was observed. However, when RA patients were stratified according to the presence or absence of CV events, an association between rs11553742*T and CV events was found (P = 0.012, odds ratio (OR) = 2.62 (1.24 to 5.53)). Likewise, the ACP1*C allele showed evidence of association with CV events in patients with RA (P = 0.024, OR = 2.43).ConclusionsOur data show that the ACP1*C allele influences the risk of CV events in patients with RA.

Is There a Role of ACP1-ADA1 Genetic Complex in Immune Reaction? Association With T1D and With Past Malarial Morbidity

In this article, we confirm the positive association of acid phosphatase locus 1 (ACP1)*A/adenosine deaminase locus 1 (ADA1)*2 gametic type with type 1 diabetes (T1D) previously reported and show a negative correlation between the frequency of this gametic type with past malarial morbidity in Sardinia. One hundred seven adult women with T1D and 385 healthy adult women from the Caucasian population of Central Italy have been studied. Data on 1384 children from the central area of Sardinia have also been reexamined. T1D subjects show a highly significant increase of ACP1*A/ADA1*2 gametic type compared with healthy subjects from the same population (P=0.003). The frequency of ACP1*A/ADA1*2 gametic type is decreasing with increasing past malarial morbidity. Because ADA1*2 allele decreases the activity of *A allele and since low ACP1 activity decreases Zeta-chain-associated protein kinase with molecular weight 70kDa (Zap70) activity resulting in weak T-cell receptor signalling an epistatic interaction involving ADA1, ACP1 and Zap70 seems a likely mechanism for the associations observed.

The Interaction of ACP1, ADA1, Diabetes and Gender in Coronary Artery Disease

IntroductionPrevious separate studies have shown associations of coronary artery disease (CAD) with acid phosphatase locus 1 (ACP1) and adenosine deaminase locus 1 (ADA1) genetic polymorphisms. Because it is known that the 2 systems interact and have important immunologic and metabolic functions, these 2 genes were both examined in the same sets of subjects. MethodTwo-hundred forty subjects with CAD, 156 subjects with cardiovascular diseases without CAD, 279 subjects with Non Insulin Dependent Diabetes Mellitus (NIDDM) without CAD and 771 consecutive healthy newborn infants have been studied. ResultsThe association of ACP1 and ADA1 with CAD depends on sex and diabetes. In particular, the association between ADA1 and CAD is present in nondiabetic subjects only, and it is dependent on sex (males), whereas the association of CAD with ACP1 is present in diabetic subjects only, and it is dependent on sex (females). ConclusionsThe fact that the association of ACP1 with CAD is evident only in diabetic subjects, whereas the association of ADA1 with CAD is evident only in nondiabetic subjects suggests an heterogeneity in the pathogenetic mechanisms leading to CAD. In addition, the association with sex that could be based on hormonal differences is in favor of heterogenity.

The effect of genetic variability on the correlation between blood glucose and glycated hemoglobin levels

The disturbing results of recent clinical trials aimed to control cardiovascular risk of diabetes by aggressive control of blood glucose prompted us to analyze the effect of genetic variability of 2 polymorphic enzymes abundant in red blood cells on the correlation between blood glucose and glycated hemoglobin (Hb). Two hundred eighty subjects with type 2 diabetes mellitus were studied. Adenylate kinase locus 1 (AK1) and acid phosphatase locus 1 were determined. Correlation between blood glucose and glycated Hb was determined for phenotypes of the 2 systems. The correlation between blood glucose and glycated Hb is higher in carriers of AK1*2 allele than in subjects with AK11 phenotype. The highest coefficient is observed in acid phosphatase locus 1 phenotypes with the highest enzymatic activity; and the lowest, in phenotypes with the lowest activity. Effects of sex, blood glucose level, age, age at onset, and duration of disease have been also considered. Our data are in agreement with recent observation in healthy subjects suggesting a role of genetic factors on glycated Hb level. If glycation of structural and functional protein is dependent not only on blood glucose level but also on genetic factors, these factors could have an important role in the susceptibility and clinical course of diabetes.

Genetic assessment of serological and biochemical markers in Bharia tribe of Chhindwara district of Madhya Pradesh

BACKGROUND:The present sero-genetic study is the first of its kind to present the baseline data of Bharia tribe of Madhya Pradesh. The main aim of this study is to provide phenotype and allele-frequency data to characterize the population genetically and to fill the void on the genetic map of Madhya Pradesh.MATERIALS AND METHODS:For this, blood samples from 92 unrelated healthy individuals of Bharia tribe from Chhindwara district (Tamia block) were collected. Hemolysates prepared were analyzed for two serological (A1A2BO and Rh) and six biochemical (adenosine deaminase, adenylate kinase locus 1, acid phosphatase locus 1, phosphoglucomutase locus 1, esterase D and glucosephosphate isomerase) parameters, following the standard electrophoretic techniques.RESULTS:The Chi-square test for goodness of fit revealed no significant deviation between the observed and expected numbers in any of the seven genetic markers, suggesting that the tribe is in genetic equilibrium. A high incidence of B allele in A1A2BO blood group and low incidence of the A1 allele, with presence of A2 in only one individual, and a low frequency of Rh(D) (Rh negative allele) was observed in serological markers. Also, no rare variant was observed for biochemical markers.CONCLUSION:Principal Component Analysis done in order to detect the genetic affinity of Bharia tribe with other populations from the adjoining states of Madhya Pradesh based on the allele frequencies, showed a close association of Bharia with Gujarat and Rajasthan. Hence, this study has been helpful in revealing the genetic structure and affinity of Bharia tribe.