MM Genotype Research Articles

Detection of alpha-1 antitrypsin gene mutations by polymerase chain reaction in patients with chronic obstructive pulmonary disease

Introduction. The alpha-1 antitrypsin deficiency is the best described genetic cause of chronic obstructive pulmonary disease. The study of the alpha-1 antitrypsin deficiency, as the most important genetic risk factor for chronic obstructive pulmonary disease, is an important step in developing a strategy for the prevention and treatment of this disease. The aim of the study was detection of homozygous and heterozygous deficient gene alleles (protease inhibitor Z and protease inhibitor S) for alpha-1 antitrypsin in the group of patients with chronic obstructive pulmonary disease with the predominance of lung emphysema, as well as determination of a positive correlation between the serum levels of alpha-1 antitrypsin and the corresponding alpha-1 antitrypsin genotype. Material and Methods. The study included 90 patients, mutually unrelated individuals, hospitalized due to lung emphysema. The control group included 10 subjects, with no clinical signs of lung emphysema, but with a family history of chronic obstructive pulmonary disease. We attempted to identify the most common deficient alleles (protease inhibitor Z and protease inhibitor S) and the concentration of alpha-1 antitrypsin in the serum of the examinees. The polymorphism between the two allelic forms, protease inhibitor Z and protease inhibitor S, was detected by real-time polymerase chain reaction. Results. Protease inhibitor MM genotype alpha-1 antitrypsin was present in all 90 patients with the diagnosis of pulmonary emphysema, and the serum levels of alpha-1 antitrypsin were within the range of reference values. In the control group, there were two cases with mutated protease inhibitor MZ genotype, and in these 2 subjects the serum level of alpha-1 antitrypsin was at the lower limit of reference values. Conclusion. In patients diagnosed with lung emphysema, protease inhibitor MM genotype of alpha-1 antitrypsin and normal serum alpha-1 antitrypsin levels, the genetically- determined deficiency of alpha-1 antitrypsin is not responsible for the development of chronic obstructive pulmonary disease.

Angiotensinogen M235T Gene Polymorphism is a Genetic Determinant of Cerebrovascular and Cardiopulmonary Morbidity in Adolescents with Sickle Cell Disease

BackgroundCerebrovascular stroke is a common critical complication of sickle cell disease (SCD). Angiotensinogen (AGT) M235T gene polymorphism is associated with risk of ischemic stroke and cardiovascular disease. AimWe investigated the potential association between angiotensinogen M235T gene polymorphism and susceptibility to cerebrovascular and cardiopulmonary complications in adolescents with SCD. MethodsForty-six patients with SCD in steady state were studied stressing on history of stroke, hydroxyurea/chelation therapy, hematological profile, and echocardiographic findings. Polymerase chain reaction-based restriction fragment length polymorphism analysis was used to detect AGT M235T gene polymorphism. Fifty sex- and age-matched healthy controls were enrolled for assessment of M235T gene polymorphism pattern. ResultsThe distribution of AGT M235T gene polymorphism was similar between SCD patients and healthy controls. The frequency of T allele of AGT M235T gene polymorphism (TT and MT genotypes) was significantly higher among patients with history of manifest stroke (P < .001). Patients with TT and MT genotypes had higher incidence of cardiopulmonary complications (P = .041) as well as higher percentage of HbS (P < .001) and lower hemoglobin level (P = .008) compared with those with MM genotype. Serum ferritin, liver iron concentration, and cardiac T2* were not related to T alleles or genotypes. Logistic regression analysis revealed that M235T genotype was a significant independent factor related to the occurrence of stroke among patients with SCD (Odds Ratio 14.05, 95% confidence interval 3.82-28.91; P = .001). ConclusionAGT M235T gene polymorphism may represent a genetic modifier to vascular morbidities in Egyptian patients with SCD.

Changes in lipid profile parameters and PON1 status associated with L55M PON1 polymorphism, overweight and exposure to tobacco smoke

Objective: The aim of our study was to investigate the effects of paraoxonase 1 (PON1) L55M polymorphism on the enzyme’s activity and concentration in the serum as well as its association with lipid profile parameters in a group of healthy persons. We also evaluated the presence of PON1 L55M polymorphism in a group of subjects exposed to tobacco smoke and with overweight or obesity on those parameters. Methods: Analysis of L55M polymorphism was done using polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (PCR – RFLP). Serum PON1 concentration and lipid profile parameters were assayed using commercial tests. PON1 activities were measured earlier elaborated procedures. Results: We observed a statistically significant difference in HDL and PON1 concentration: the highest in the LL genotype and the lowest in the MM genotype with the LM genotype having an intermediate concentration. L55M polymorphism influence on PON1 arylesterase and phosphotriesterase activity, whereas PON1 lactonase activity did not differ in all polymorphic variant groups. Exposure to tobacco smoke and overweight or obesity additionally disorder above mentioned parameters. Overweight and obesity in LM and MM genotype could be associated with higher PON1 phosphotriesterase activity. It is also possible that MM genotype could be a determinant of smoking addiction. Conclusions: L55M polymorphism, like exposure to tobacco smoke and overweight, disorders PON1 status and lipid profile parameters; therefore, it could be a crucial risk factor for the development of many metabolic disorders.

Genotypes of Common Polymorphisms in the PON1 Gene Associated with Paraoxonase Activity as Cardiovascular Risk Factor

Paraoxonase-1(PON1) exhibits hydrolytic activity and prevents the oxidation of high and low-density lipoproteins. Polymorphisms in the PON1 gene have been associated with variations in paraoxonase activity and with the risk of coronary artery disease (CAD). This study analyzed the association between the frequencies of genotypes of the L55M and Q192R SNPs in the PON1 gene with the PON1 activity and with CAD risk factors. Women, determined by body composition, biochemical markers, and arylesterase (AREase) and paraoxonase (CMPase) activities were studied. Genotyping of L55M and Q192R polymorphisms was performed by TaqMan. Seventeen studies were used in the meta-analysis. A significant decrease in PON1 activity in carrying the LM/MM and QQ genotypes is identified, correlations are found between the AREase activity with glucose, cholesterol and atherogenic risk index. Carriers of the LM or MM genotype were related with obesity (OR=1.6; p=0.039), and the MQ haplotype has an effect on the decrease in AREase (β=‒22.4; p<0.001) and CMPase (β=‒3.8; p<0.001). In addition, a lower proportion of Native American admixture was observed in women with LM or MM genotype, while it was higher for the European proportion compared with the LL genotype (p<0.001). The LL-L55M and QR-Q192R genotypes are identified as the most frequently in the different states or cities of the country, and genotypic proportions are different, probably depending on the genetic structure of the populations. The association that is reported more frequently in the different studies is with enzymatic activity.

27 RELATIONSHIP BETWEEN GENETIC POLYMORPHISM OF ANGIOTENSINOGEN M235T GENE AND ESSENTIAL HYPERTENSION AMONG ETHNICS IN SOUTHEAST SULAWESI

Background: The studies on genetic polymorphism of angiotensinogen M235T gene conducted in several countries showed that the emergence of allele 235T among Asians had increased the risk of hypertension compared to Caucasians. Nevertheless, relations between angiotensinogen gene polymorphism and essential hypertension risk on intra-populations of asian people between ethnics is still less consistent. Objective: This study aimed to examine the relationship in polymorphism of angiotensinogen M235T gene as a risk factor causing essential hypertension among ethnics in Southeast Sulawesi. Method: This research used cross sectional study design. Sixty-one genetic samples (peripheral venous blood from 53 hypertensive and 8 normotensive subjects) were processed through polymerase chain reaction and restriction fragment length polymerase. Results: Tolaki ethnic who had homozygous TT genotype were 27 samples (44.3% of total sample) and homozygous MT genotype were 6 samples (9.8%). Muna ethnic who had homozygous TT genotype were 22 samples (36.1%) and there were no heterozygous MT genotype. Buton ethnic who had homozygous TT genotype were 5 samples (8.2%) dan heterozygous MT genotype was found in 1 sample (1.6%). Overall, the numbers of homozygous TT genotype were 54 samples (88.5%), homozygous MT genotypes were 7 (11.5%) and no subject was homozygous MM genotype. Among the hypertensive group, 46 were TT genotype and 7 were MT genotype. In the normotensive group (all 8 samples), only TT genotype was found (chi-square 1.94, p-value 0.275). Conclusion: This study concluded that there was no relationship between polymorphism of Angiotensinogen M235T gene and essential hypertension among ethnics in Southeast Sulawesi.

Evaluation of Association Between Q192R and L55M Genetic Polymorphisms of PON1 and Serum Paraoxonase-1 Activity in Healthy Individuals, a Meta-Analysis

Abstract Background and Aims: Several studies have reported the alteration of the paraoxonase 1 (PON1) enzyme activity in various diseases, including diabetes mellitus. The Q192R and L55M are two genetic variations in the coding region of PON1. To evaluate the relationship between these polymorphisms and the alteration in serum paraoxonase activity, the present meta-analysis was carried out. Material and Methods: Eligible studies published before October 2017 was identified in several databases. The paraoxonase activity in subjects with variant alleles of the study polymorphisms were normalized using the activity of the QQ or LL genotypes. The pooled mean effect of alterations in activity level and its 95% confidence intervals (95% CI) was calculated. Results: Thirty-two studies including 11532 healthy participants were used for the present meta-analysis. The paraoxonase activity was increased in the QR and RR genotypes. This elevation was greater among Caucasians than those among Asians and Africans. The activity in the LM and MM genotypes compared with the LL genotype were decreased, this reduction in Caucasians was greater than Africans. Conclusions: At least in part other PON1 polymorphisms and environmental factors may accounts for heterogeneity between studies.

Paraoxonase 1 (PON1)-L55M among common variants in the coding region of the paraoxonase gene family may contribute to the glycemic control in type 2 diabetes

ObjectiveGenome studies have shown that the genes encoding paraoxonase 1 (PON1) and PON2 are associated with glucose metabolism. The goal of this study was to simultaneously evaluate the association between functional variants in PON1 and PON2 genes and susceptibility for type 2 diabetes (T2D) and determine whether they can affect glycemic control. MethodsWe performed a case-control study with 145 newly diagnosed patients with T2D and 148 controls. The common variants including PON1-Q192R, PON1-L55M and PON2-S311C were genotyped by PCR-based RFLP. A mismatch-PCR/RFLP was applied for genotyping the PON2-A148G variant. ResultsThe variant PON1-Q192R in males (OR = 2.55, 95%CI 1.16–5.69, p = 0.023) and PON2-A148G in females (OR = 1.56, 95%CI 1.00–2.44, p = 0.059) were associated with T2D. Compared with the LL genotypes of PON1-L55M, HbA1c levels were significantly lower in the LM genotypes (p = 0.01) and MM genotypes (p = 0.032) in patients. Multiple linear regression analyses showed that among the study variants only the PON1-L55M variant as an independent variable significantly associated with glycemic control. This variant significantly influenced glycemic control in patients with poor glycemic control so that it was better with the following order: LL < LM < MM. Based on gamma correlation, there was a significant inverse association between the number of M alleles of the PON1-L55M and HbA1c levels (r = −0.261, p = 0.001). ConclusionsSex should be considered a confounding variable in association studies on the variants PON1-Q192R and PON2-A148G in T2D. Patients sharing the 55 M allele were prone to having good glycemic control. Our findings provide genetic evidence that the PON1-L55M variant may be a factor contributing to glycemic control.

F189. PERSONALIZED MEDICINE: ESTIMATING THE IMPACT OF GENOTYPES ON ANTIPSYCHOTIC EFFICACY USING A QUANTITATIVE SYSTEMS PHARMACOLOGY APPROACH

BackgroundCNS disorders are lagging behind other indications such as oncology in implementing genotype-dependent treatment algorithms for personalized medicine. This is due to the limited knowledge about the interaction of the relevant biology and the drug’s pharmacologyMethodsWe applied a mechanism-based computer model of a cortico-striatal-thalamocortical loop of the dorsal motor circuit that has been calibrated with clinical data on antipsychotic treatment in schizophrenia patients (Spiros, Roberts et al. 2017). The Quantitative Systems Pharmacology (QSP) model is based on the appropriate connections between basal ganglia regions and consists of 220 neurons (8 different cell types), 3500 synapses and implementations of 32 CNS active targets, based on their unique locations and coupling with intracellular pathways. COMTVal156Met, 5-HTTLPR rs 23351 s/L and D2DRTaq1A1 genotypes are implemented using human imaging data in non-medicated human volunteersResultsThe dose-dependent antipsychotic effect for risperidone, aripiprazole and paliperidone is sensitive to the COMT genotype with the MM genotype having the greatest difference with the wild-type. Interestingly the 5-HTTLPR genotype interacts with the COMT genotype: this difference is positive for 5-HTTLPRss and negative for 5-HTTLPR LL. Olanzapine, quetiapine, clozapine and haloperidol are affected much less. The D2DRTaq1A allele interacts in a complex way with the COMT genotype with haloperidol, aripiprazole and risperidone and with the 5-HTLLPR genotype for haloperidol, aripiprazole, risperidone and paliperidone. These effects are anticipated to be detectable in clinical settings.DiscussionThe QSP platform predicts strong and complex genotype-dependent interactions with aripiprazole, risperidone, haloperidol and paliperidone and to a much smaller degree with olanzapine, quetiapine and clozapine. These predictions could in principle be verified in clinical setting and could lead to rational personalized treatment guidance

Investigation of antioxidant enzyme polymorphism in chronic obstructive pulmonary disease patients

Background: Antioxidant system enzyme activity and polymorphism were investigated in Chronic Obstructive Pulmonary Disease (COPD), which is increasingly prevalent both in the world and our country. Methods: Malondialdehyde (MDA) was measured to determine lipid peroxidation, while Catalase (CAT), Paraoxonase (PON) and Superoxide Dismutase (SOD) enzyme activities were measured to determine antioxidant activity. For molecular analysis, leukocytes were separated and DNA was isolated from cell nuclei and the targeted genes were amplified by using PCR. Targeted base changes were detected by the restriction fragment length polymorphism technique. Results: Evaluating CAT polymorphism, there was 35 (35%) TT, 52 (52%) TC and 13 (13%) CC genotypes in the control group, as 38 (38%) TT, 40 (40%) TC and 22 (22%) CC genotypes in the patient. In SOD, there were 32 (32%) TT, 49 (49%) TC, 19 (19%) CC genotypes in the control group, as 34 (34%) TT, 50 (50%) TC and 16 (16%) CC genotypes in the patient. In PON55, there were 50 (50%) LL, 38 (38%) LM, 12 (12%) MM genotypes in the control group, as 39 (39%) LL, 49 (49%) LM and 12 (12%) MM genotypes in the patient. In PON192, there were 77 (77%) QQ, 21 (21%) QR, 2 (2%) RR genotypes in the control group, as 66 (66%) QQ, 29 (49%) QR, 5 (5%) RR genotypes in the patient. There was no significant difference in genotype distribution for CAT, SOD, PON55 and PON192 polymorphisms between groups. Conclusion: In conclusion, COPD patients were found to have a deficiency in the antioxidant defense system. This will lead to the development of oxidative stress in patients and the complications of COPD. There was no polymorphic difference between the control group and South African patients living in Adiyaman in COPD whose genetic characteristics were not fully explained.

TLR4 Asp299Gly and Thr399Ile and TLR2 intron 2 microsatellite gene polymorphism in patients with acute biliary pancreatitis: Does it cause the disease?

There has been coverage of Toll-like receptor 4 and Toll-like receptor 2 gene polymorphisms in inflammatory episodes in a number of studies. In view of the inflammatory nature of acute pancreatitis, we aimed to determine the predictive value of mutations in Asp299Gly and Thr399Ile of the Toll-like receptor 4 gene, and the intron 2 microsatellite polymorphism of the Toll-like receptor 2 gene on the occurrence of acute biliary pancreatitis. The study included 86 patients for the Toll-like receptor 4 Thr399Ile polymorphism, 100 patients for the Toll-like receptor 4 Asp299Gly polymorphism with acute biliary pancreatitis, and 101 healthy volunteers. At the same time, 93 patients and 92 healthy volunteers were included in the study to research the Toll-like receptor 2 intron 2 microsatellite polymorphism. Genotypes were determined using the restriction fragment length polymorphism analysis of PCR products and by an allele-specific PCR. The Toll-like receptor 4 Thr399Ile homozygotes mutant variants (p=0.005) and Toll-like receptor 2 MM genotype (p<0.001) were detected with a significantly higher frequency in patients with acute biliary pancreatitis than in the healthy blood donors. The Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms and the Toll-like receptor 2 intron 2 microsatellite polymorphism are statistically associated with ABP.

Angiotensin II receptor type 1 A1166C modifies the association between angiotensinogen M235T and chronic kidney disease.

Single nucleotide polymorphisms (SNPs) in renin-angiotensin system (RAS) genes are associated with RAS imbalance and chronic kidney disease (CKD). We performed a case-control study and meta-analysis to investigate the association between angiotensinogen (AGT) M235T polymorphism and CKD. A total of 634 patients with end-stage renal disease and 739 healthy controls were studied. We also searched PubMed and the Cochrane Library to identify prospective observational studies published before December 2015. We found that the TT and MT genotypes were associated with a higher risk of CKD than the MM genotype (odds ratio [OR]: 3.56; 95% confidence interval [CI]: 1.14–11.16 and OR: 2.93; 95% CI: 0.91–9.46, respectively). Thirty-eight study populations were included in the meta-analysis. The T allele was associated with a higher risk of CKD than the M allele in all populations (OR: 1.19; 95% CI: 1.08–1.32). The OR was 1.33 in Asians (95% CI: 1.06–1.67) and 1.10 in Caucasians (95% CI: 1.02–1.18). Evaluation of gene-gene and gene-environment interactions using epistasis analysis revealed an interaction between AGT M235T and angiotensin II receptor type 1 A1166C in CKD (OR: 0.767; 95% CI: 0.609–0.965). Genetic testing for CKD in high-risk individuals may be an effective strategy for CKD prevention.

A1AT polymorphisms may be associated with clinical characteristics of retrovirus infections in a mixed ethnic population from the Brazilian Amazon region

ObjectivesThis study investigated the association of alpha-1-antrypsin deficiency (A1AT; S and Z polymorphisms) with HIV-1 and HTLV-1 infection. MethodsBlood samples from 201 HIV-1-infected and 115 HTLV-1-infected individuals were examined and compared with those from 300 healthy controls. Genotyping of A1AT (S and Z) and quantification of plasma viral load were performed using RT-PCR, and the CD4+/CD8+ T-cell count was determined by flow cytometry. ResultsThe wild-type MM genotype showed the highest frequency in each of the three groups investigated. SS and ZZ homozygous genotypes (variants) were observed only among HTLV-1 patients and controls, respectively. Genotype MS was significantly less frequent in HTLV-1-positive persons than in controls. Statistically significant differences were observed when comparing genotype frequencies between symptomatic and asymptomatic HTLV-1-infected persons. The distribution of plasma HIV-1 viral load among individuals with different genotypes of A1AT polymorphism also differed significantly. ConclusionsThe results suggest that A1AT polymorphisms may be associated with human retrovirus infections when dealing with an ethnically mixed population from the Amazon region of Brazil.

Association between ACE and AGT polymorphism and cardiovascular risk in acromegalic patients.

Whether the renin-angiotensin-aldosterone system plays a role or not in the development of cardiovascular morbidity in acromegaly patients is unknown. The aim of the study was to investigate the association between ACE (I/D) and AGT (M235T) gene polymorphisms and cardiovascular and metabolic disorders in the acromegaly. The study included one hundred and seventeen acromegalic patients (62F/55M, age: 50.2 ± 12.3 years) and 106 healthy controls (92F/14M, age: 41.4 ± 11.3 years). PCR method was used to evaluate the prevalence of ACE and AGT genotype. The genotypes of ACE polymorphism in acromegalic patients were distributed as follows; 41.0% (n: 48) for DD, 44.4% (n: 52) for ID and 14.5% (n: 17) for II genotype. The control group had significantly different distribution of the ACE polymorphism [48.1% (n: 51) for DD, 25.5% (n: 27) for ID and 26.4% (n: 28) for II genotype]compared to acromegalic group. Regarding AGT polymorphism, AGT-MT genotype was seen in 88.9% of the acromegalic patients while MM and TT genotype (9.4% and 1.7%, respectively) were present in the rest. The controls had similar distribution of the AGT genotype with the acromegaly group (80.2% MT genotype, 15.1% MM genotype and 4.7% TT genotype). Due to the small number of patients with TT allele (n: 2), T carriers for AGT genotype (AGT-MT+TT) were subgrouped and compared to those with AGT-MM group. ACE-DD, ID and II groups had similar anthropometric measures, blood pressure values and baseline GH and IGF-1 levels. Significantly higher baseline GH levels were found in AGT-MM group compared to T allele carriers [40 (16-60) vs. 12 (5-36)µg/L, p < 0.05]. The compared groups in both polymorphisms had similar fasting plasma glucose levels. Patients with ACE-II genotype had significantly higher HDL-C levels compared to those with ACE-DD and ACE-ID polymorphisms (p < 0.05) whereas there was no significant difference in lipid profile between AGT-MM group and AGT-T allele carriers. Moreover, the compared groups in both polymorphisms had similar distribution of hyperlipidemia, hypertension, impaired glucose metabolism (prediabetes or type 2 diabetes mellitus) and coronary artery disease. In terms of echocardiographic parameters, systolic and diastolic function was similar among the groups in ACE and AGT genotypes. Interestingly, AGT-MM group had higher mitral inflow Apeak values than T allele carriers (0.94 ± 0.46 vs. 0.73 ± 0.20; p = 0.051). No significant difference was observed in LV mass index values in acromegalic patients among the groups in both polymorphisms. Both ACE (I/D) and AGT (M235T) gene polymorphisms do not seem to have a significant effect on the development of clinical properties or cardiovascular comordities of acromegalic patients.

The Gene Variants of Maternal/Fetal Renin-Angiotensin System in Preeclampsia: A Hybrid Case-Parent/Mother-Control Study

Preeclampsia (PE) is a common pregnancy-related complication, and polymorphisms in angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and angiotensin II type 1 receptor (AT1R) are believed to contribute to PE development. We implemented a hybrid study to investigate the influence of maternal and fetal ACE I/D, ACE G2350A, AGT M235T, AGT T174M, and AT1R A1166C polymorphisms on PE in Han Chinese women. Polymorphisms were genotyped in 1,488 subjects (256 patients experiencing PE, along with their fetuses and partners, and 360 normotensive controls with their fetuses). Transmission disequilibrium tests revealed that ACE I/D (P = 0.041), ACE G2350A (P = 0.035), and AT1R A1166C (P = 0.018) were associated with maternal PE. The log-linear analyses revealed that mothers whose offspring carried the MM genotype of AGT M235T had a higher risk of PE (OR = 1.54, P = 0.010), whereas mothers whose offspring carried the II genotype of ACE I/D or the GG genotype of ACE G2350A had a reduced risk (OR = 0.58, P = 0.039; OR = 0.47, P = 0.045, respectively). Our findings demonstrate that fetal ACE I/D, ACE G2350A, AGT M235T, and AT1R A1166C polymorphisms may play significant roles in PE development among pregnant Han Chinese women.

Novel diagnostic technologies for clinical and frontline use: Advanced diagnostics based on molecular markers and analysis technologies has been improving diagnosis across a wide range of diseases.

Misdiagnosis is a major problem at all levels of health care causing unnecessary pain or even death as it prevents efficient, timely, and adequate treatment. In the case of infectious diseases, for instance, identification of the wrong pathogen might lead to incorrect prescription of antibiotics. While reliable data on the full extent of misdiagnosis are elusive, some evidence of the problem's scale came from a meta‐analysis of deaths within US intensive care units (ICUs), which found that 40,500 adult patients in the USA may die each year as a result of a misdiagnosis [1]. An earlier, more comprehensive, study based on searching the MEDLINE (1950–2007) and EMBASE (1980–2007) electronic databases for articles about diagnostic error or delay in primary care also found that misdiagnosis was a significant issue, although the reasons varied with each condition [2]. Moreover, many diseases, in particular rare diseases, are hard to diagnose as physicians are often unfamiliar with the symptoms; alternatively, the symptoms might be vague or untypical, as can happen with some autoimmune disorders. Many cancers in their early stages do not even show any symptoms, which prevents timely and effective treatment. There are also complex disorders that present highly varied symptoms that can lead doctors in the wrong direction, at least at first. Not surprisingly, there is an immense interest in molecular‐level diagnostics that promise to deliver far more accurate and rapid diagnoses without relying on interpreting symptoms. While this can raise new challenges, such as poor‐quality samples or analyzing complex data sets, molecular diagnostics has made progress across a range of clinical conditions, including infectious diseases and some cancers, through identification of characteristic molecular markers. A wide variety of diseases could also be diagnosed using next‐generation sequencing (NGS), including solid cancers or rare diseases of genetic origin. NGS …

Association between MspI calpastatin gene polymorphisms, growth performance, and meat characteristics of Awassi sheep

The association between the ovine calpastatin gene (CAST) genotypes, growth performance and meat characteristics of Awassi sheep was investigated. Homozygous (MM) and heterozygous (MN) genotypes of the CAST were obtained by RFLP, using Awassi ram lambs (age=7 to 14 days n= 80).A fattening trial was conductedusing 10 ram lambs MspI - of CAST genotypes (5 lambs from each genotype) (homozygous (MM) and heterozygous (MN). Lambs were weighed at the beginning of the experiment and the subsequent weights were measured biweekly before the morning feeding throughout the duration of the experiment. At the end of the fattening period, all lambs were slaughtered to evaluate carcass characteristics and meat quality. The results showed a significant association between CAST genotypes and growth rate and final body weight showing that lambs of the MN genotype had a higher average daily gain and final body weight compared to lambs of the MM genotype. The CAST gene genotypes showed a significant effect on some carcass components and meat quality parameters indicating that MN genotype showed lower total bone and higher meat to bone ratio than the MM genotype in the dissected leg cut. Furthermore, the MN genotype had a higher longissimus muscle weight compared to MM animals. Meat quality analysis showed that MN genotype lambs had higher shear force, lower cooking loss and lightness. It can be concluded that the CAST gene can be considered as one of the genes that control growth performance and meat quality traits.

The Association of Angiotensinogen (AGT M235T) Gene Polymorphism and Essential Hypertension in Thai Post-Menopausal Women

Objectives: This study aims to determine the relationship between angiotensinogen (AGT) M235T polymorphism and hypertension among post-menopausal Thai women. Materials and Methods: Case-control study was conducted. The study group was those who had hypertension or previously diagnosed and, the control were those who had no hypertension. Blood samples were taken for AGT M235T allelic characterization using allele specific oligonucleotides (ASO) PCR. Results: Of 255 post-menopausal women, 128 had hypertension, regarded as “hypertension group”, the other 127 without hypertension, regarded as “control group”. The presence of AGT M235T polymorphism was 76.5% for homozygous mutation (73.4% for hypertension group and 79.5% for control group), 21.2% for heterozygous mutation (25.0% for hypertension group and 17.3% for control group, respectively) and 2.4% for homozygous wild-type (1.6% for hypertension group and 3.2% for control group, respectively). Distribution of MM, MT and TT genotypes was not significantly different between both group (p=0.251). Conclusions: Interestingly, overall TT genotype was much higher than that of TM and MM in post-menopausal Thai women. AGT M235T polymorphism was not significantly associated with hypertension, though TT genotype tended to give a small risk. They may not serve as a good genetic marker for essential hypertension among Thai population.

Polymorphism in exon 3 of myostatin (MSTN) gene and its association with growth traits in Indian sheep breeds

The polymorphism of myostatin (MSTN) gene was analysed as a genetic marker for growth traits in Madras Red and Mecheri sheep breeds of Tamil Nadu. PCR-RFLP revealed a SNP G5622C in exon 3 and was confirmed by sequencing. The breed-wise genotypic and allelic frequencies observed for MM genotype were 0.417 and 0.486; and Mm were 0.583 and 0.514 in Madras Red and Mecheri breeds respectively. The estimated allelic frequencies for M and m in Madras Red and Mecheri breeds were 0.7085 and 0.2915; and 0.7430 and 0.2570 respectively. Madras Red sheep with homozygous (MM) genotypes were significantly (P<0.05) heavier than heterozygous (Mm) genotype by 1.162kg and 1.227kg at nine and 12 months weight respectively. However, no significant effect was observed for birth, weaning (three months) and six months weight in the same breed. There was no significant difference in mean birth, weaning, six, nine and 12 months weight between MM and Mm genotypes in Mecheri sheep.

Novel strain properties distinguishing sporadic prion diseases sharing prion protein genotype and prion type

In most human sporadic prion diseases the phenotype is consistently associated with specific pairings of the genotype at codon 129 of the prion protein gene and conformational properties of the scrapie PrP (PrPSc) grossly identified types 1 and 2. This association suggests that the 129 genotype favours the selection of a distinct strain that in turn determines the phenotype. However, this mechanism cannot play a role in the phenotype determination of sporadic fatal insomnia (sFI) and a subtype of sporadic Creutzfeldt-Jakob disease (sCJD) identified as sCJDMM2, which share 129 MM genotype and PrPSc type 2 but are associated with quite distinct phenotypes. Our detailed comparative study of the PrPSc conformers has revealed major differences between the two diseases, which preferentially involve the PrPSc component that is sensitive to digestion with proteases (senPrPSc) and to a lesser extent the resistant component (resPrPSc). We conclude that these variations are consistent with two distinct strains in sFI and sCJDMM2, and that the rarer sFI is the result of a variant strain selection pathway that might be favoured by a different brain site of initial PrPSc formation in the two diseases.

Patatin-like phospholipase domain-containing protein 3 (PNPLA3): A potential role in the association between liver disease and bipolar disorder

ObjectiveDue to the increased prevalence of liver disease in patients with bipolar disorder, we examined the potential role of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant among individuals with bipolar disorder and those with no mood disorder. MethodsWe used the National Health and Nutrition Examination Survey (NHANES) database (aged 15–39 years) to identify a group of individuals with a bipolar diagnosis and a control group of individuals with no mood disorder. A total of 1931 individuals were randomly selected, one from each family containing information on the PNPLA3 genotype to be used in the analysis. ResultsAnalyses revealed individuals with the recessive variant genotype (MM) had an adjusted odds ratio for bipolar disorder of about 4.6 compared to individuals with either IM or II genotypes of the PNPLA3 variant. Limitations and conclusionsLimitations of this study include the use of a lay-administered survey in for diagnosis of bipolar disorder in NHANES. The association between the PNPLA3 variant and bipolar disorder may help guide further work on medication effectiveness, treatment options, prevention approaches, and understanding potential medication side effects among specific subgroups of individuals with the MM genotype.