AC Genotype Research Articles

The identification of a novel SNP in the resistin (RETN) gene associated with growth traits in Karakul and Awassi sheep

Resistin is one of the most important adipocytokines in mammalian cells due to its involvement in insulin resistance, obesity, and autoimmune diseases. Resistin is encoded by RETN gene that is primarily expressed in adipose tissues. Mutations in this gene have been associated with several productive traits in animals. This study was conducted to assess the possible biomarker capacity of RETN by evaluating its association with growth traits in two economically important sheep in the Middle East. Genotyping was conducted using PCR-single strand conformation polymorphism (SSCP), and the polymorphism of RETN was associated with several growth traits for three months intervals starting from birth until one year of age. In a total of 190 Karakul sheep and 245 Awassi sheep, only one SNP (233A > C) was detected in the RETN gene. The identified novel SNP showed significant associations with all growth traits at the ages of six, nine, and twelve months. At the age of six months onward, lambs with AC and CC genotypes showed respectively lower body weight and length, chest and abdominal circumferences, and wither and rump heights than those with AA genotype. Dueto the remarkable association between RETN;233A > C and lower growth traits, this genotype is suggested as apromising markerto assess growth traits in Karakul and Awassi sheep. This is the first study that demonstrated the importance of RETN as a possible tool for evaluating growth traits in two breeds of sheep with a possibility to be applied to other breeds via large-scale association analysis.

Investigation of the Roles of MTHFR (C677T and A1298C) and MMP-2 (-1306C>T ) Variations in Bladder Cancer Development.

Bladder cancer is a complex malignancy and has been associated with high morbidity. Since susceptibility to bladder cancer development differs between individuals, determining the roles of MTHFR and MMP-2 gene variations associated with this cancer is important for analyzing differences in individual susceptibility. In this study, we aimed to investigate the role of MTHFR and MMP-2 gene variations in the development of bladder cancer in the Thrace region of Turkey. One hundred seventy-nine blood samples were collected, including 98 patients with bladder cancer and 81 healthy controls. DNA extraction was carried out with blood samples. Polymerase chain reaction-restriction fragment length polymorphism was applied to detect MTHFR C677T (rs 1801133), MTHFR A1298C (rs 1801131), and MMP-2 (-1306C>T) (rs 243865) gene variants. For the MTHFR A1298C gene variation, CC genotype was the genetic risk factor (P=.0001), while AC genotype was the protective factor (P< .0001) in the development of bladder cancer. For the MMP-2 (-1306C>T) gene variation, TT genotype (P < .0001) and T allele (P=.0006) were genetic risk factors, while AC genotype (P=.0009) was the protective factor in the development of bladder cancer. For C677T/A1298C gene variations, CC-CC combined genotype was the genetic risk factor (P=.009), while CT-AC and CC-AC combined genotypes were potential protective biomarkers (P=.013 and P < .001, respectively). In our study, TT genotype and T allele were determined as genetic risk factors for MMP-2 (-1306C>T) gene variation. For C677T/A1298C gene variations, CC- CC combined genotype was detected as the genetic risk factor in the development of bladder cancer.

The Associations of Single Nucleotide Polymorphisms of the COL3A1, COL6A5, and COL8A1 Genes with Atopic Dermatitis.

The pathophysiology of atopic dermatitis (AD) is complex, multifactorial, and not fully understood. Genes encoding collagens, the most abundant proteins in the extracellular matrix (ECM), may play a potential role in the pathogenesis of AD. Our study aimed to estimate the associations between Col3A1/rs1800255, Col6A5 /29rs12488457, and Col8A1/rs13081855 polymorphisms and the occurrence, course, and features of AD in the Polish population. Blood samples were collected from 157 patients with AD and 111 healthy volunteers. The genotype distribution of the investigated collagens genes did not differ significantly between the AD and control subjects (p > 0.05). The AA genotype of Col3A1/rs1800255 was significantly associated with the occurrence of mild SCORAD (OR = 0.16; 95% Cl: 0.03-0.78; p = 0.02) and mild pruritus (OR = 18.5; 95% Cl: 3.48-98.40; p = 0.0006), while the GG genotype was significantly associated with severe SCORAD (OR = 6.6; 95% Cl: 1.23-32.35; p = 0.03). Regarding Col6A5/29rs12488457 polymorphism, the average SCORAD score was significantly lower in the group of patients with genotype AA than in patients with the AC genotype (39.8 vs. 53.4; p = 0.04). Nevertheless, both average SCORAD scores were high, and represent the moderate and severe grades of the diseases, respectively. The single nucleotide polymorphisms (SNPs) of COL3A1/ rs1800255 and Col6A5/29rs12488457 seem to be associated with AD courses and symptoms, suggesting new disease biomarkers. The modulation of collagens, the major component of the ECM, may serve as a therapeutic target of AD in the future.

Interleukin -37 in rheumatoid arthritis: Correlation with clinical severity and genetic polymorphisms in Mosul city, Iraq

The contribution of anti-inflammatory cytokines to rheumatoid arthritis (RA) is not fully comprehended. In the current research we assessed the serum concentration of interleukin (IL)-37 anti-inflammatory cytokine in RA, studied its association to disease activity score 28 (DAS28) and investigated single nucleotide polymorphism (rs2723176) of IL-37 gene as a threat for RA development. The case-control study included 60 RA patients and 30 normal control individuals. Serum IL-37 was assessed by ELISA and genotyped by "sequence-specific primer-polymerase chain reaction (SSP-PCR)". The mean IL-37 was elevated in RA patients (69.42 ng /l ± 62.99) compared to control individuals (14.66 ng /l ± 23.58, p < 0.001). IL-37 tended to increase with age where highest levels were noted in patients more than 60 years (p = 0.037). No Gender influence was found on IL-37 level (p>0.05). At best cut-off value of 31.5 ng/ l, IL-37 had a sensitivity of 73.3% and specificity of 83.3%. No correlation of IL-37 with DAS 28 score was observed (r=0.1497, p=0.2535). For IL-37 (rs2723176) gene polymorphism, C/C genotype was prevailing in both RA (90%) and normal controls (93.3%) compared to A/C or A/A. Also, no variation was found between patents and controls in regard to C/C genotype (OR = 0.643, 95% CI (0.122-3.39, p=0.603). The mean IL-37 concentration in RA patients with C/C genotype (59.70± 67.92) was not different from AC genotype (80.54± 94.18, p=0.4748). We concluded that serum IL-37 had the implication as a diagnostic marker in RA. However, it did not correlate with clinical severity of the disease. Meanwhile, IL-37 (rs2723176) gene polymorphism did not seem to be as a risk factor for RA, nor contributed to the increase of IL-37 level among patients.

IRF6 and FGF1 polymorphisms in non-syndromic cleft lip with or without cleft palate in the Polish population.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is the most common developmental defect that significantly affects the morphology and function of the stomatognathic system in children. The etiology of these birth defects is multifactorial, and single nucleotide polymorphisms (SNPs) in IRF6 and FGF1 have been associated with NSCL/P. This study aimed to evaluate whether SNPs in IRF6, namely rs2013162, rs642961, rs2235373, and rs34010 in FGF1, are associated with NSCL/P occurrence in the Polish population. The study included 627 participants: 209 children with NSCL/P and 418 healthy controls. DNA was isolated from saliva in the study group and from umbilical cord blood in controls. Genotyping of polymorphisms was performed using quantitative PCR. There was no statistically significant association of IRF6 gene variants with NSCL/P occurrence, although for rs2013162, AA genotype, odds ratio (OR) = 1.16 and for AC genotype, OR = 0.83; for rs642961, AA genotype, OR = 0.84 and for AG genotype, OR = 1.41; and for rs2235373, AA genotype, OR = 0.79 and for AG, OR = 0.85. In the instance of rs34010 polymorphism in FGF1, the presence of the AA genotype was statistically significant in reducing the risk of NSCL/P (OR = 0.31, p = 0.001). Genetic variation in FGF1 is an important risk marker of NSCL/P in the Polish population, which cannot be stated for the polymorphisms in the IRF6 gene.

Türk çiftlerde infertilite ve metilentetrahidrofolat redüktaz genotipleri arasındaki ilişki

Purpose: Infertility is described as unexplained when all of the tests of a basic infertility evaluation return within normal limits and present in 15% of infertile couples. Some studies indicate that there is an association between methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) mutations and unexplained infertility in male or female grown adults. The objective of this study was to analyze the distributions of MTHFR’s C677T and A1298C genotypes in couples with unexplained fertility problems (UFP) and healthy controls.&#x0D; Materials and Methods: Two common variants C677T and A1298C of the MTHFR gene were screened in infertile couples (n =60 for C677T polymorphism; n=62 for A1298C polymorphism) and controls from the Cukurova region of Turkey. C677T and A1298C mutations in the MTHFR gene were detected by the SNP analysis (Fragment analysis) kit of the multiplex PCR amplification/ligation products. Homocysteine levels (in serum) were determined by the human hcy ELISA kit and folate values were determined by the Beckman coulter Unicel DxI 800 chemiluminescence test kit at the Central Laboratory of Balcali Hospital in Cukurova University.&#x0D; Results: In this study, an association between unexplained infertility and MTHFR C677T polymorphism was not found. However, we found an association between MTHFR A1298C polymorphism and males with UFP (%7) and controls (%19). A statistically significant difference was observed between the infertile and control groups regarding i) the folate and homocysteine values of MTHFR C677T heterozygous individuals; ii) the homocysteine values of the MTHFR C677T normal individuals; iii) the homocysteine values of MTHFR A1298C heterozygous, normal and homozygous individuals; iv) the MTHFR C677T heterozygous and normal individuals; v) the homocysteine values of MTHFR C677T normal individuals; vi) the folate values of the MTHFR A1298C heterozygous and normal individuals.&#x0D; Conclusion: The etiopathogenesis of unexplained infertility remains largely unexplored. However, the relationship of the folate/homocysteine findings with the MTHFR polymorphisms under study is not clear. The results of our study support a relationship between the MTHFR A1298C polymorphism and male fertility problems.

Association between HULC gene locus rs7763881 polymorphism and recurrence and metastasis after radical resection in hepatocellular carcinoma

Objective: To investigate the association between the expression of long non-coding RNA genes and the HULC rs7763881 polymorphism, recurrence, and metastasis after radical resection in patients with hepatocellular carcinoma (HCC). Methods: Paraffin tissue samples were selected from 426 cases diagnosed with HCC between January 2004 to January 2012. The expression of different genotypes of HULC gene locus rs7763881 in paraffin tissues was detected by PCR, and the association between different genotype expressions and clinical case characteristics of HCC [gender, age, TNM stage, alpha-fetoprotein, tumor maximum diameter (cm), vascular invasion, tumor capsule, tumor grade] was analyzed. Cox proportional risk regression model was used to analyze the correlation between different genotypes and clinicopathological features, prognosis, and recurrence. Survival analysis between different genotypes was performed using the Kaplan-Meier method for a parallel log-rank test. Results: There were 27 (6.3%) cases in the whole group who lost to follow-up. A total of 399 (93.7%) specimens were included in the study, and 105 (26.3%), 211 (52.9%) and 83 (20.8%) were included in the rs77638881 AA, AC, and CC genotypes, respectively. Kaplan-Meier curve showed that the postoperative overall survival and recurrence-free survival rate were significantly higher in patients with the AA than AC/CC genotype (P < 0.05). Univariate analysis showed that the AC/CC genotype was closely related to tumor vascular invasion and recurrence or metastasis of HCC (P < 0.05). Cox multivariate analysis results showed that patients with the AA genotype were taken as references, and the results showed that the risk of recurrence and metastasis in patients with the CA/CC genotype increased to varying degrees, with statistical significance (P < 0.05). Conclusion: The rs7763881 polymorphic loci located on the HULC gene are closely related to HCC recurrence and metastasis after radical resection. Thus, it may be an indicator for evaluating HCC recurrence and metastasis.

MTHFR A1298C polymorphism: a predictor of reduced risk of preeclampsia in Punjab, Pakistan

ABSTRACT Objectives This study aimed to investigate the genetic association between MTHFR (A1298C) SNP and preeclampsia (PE) in Punjab, Pakistan. Methods A sample of 80 pregnant women (40 healthy pregnant women and 40 with PE) was pooled for genotyping MTHFR A1298C polymorphism by using the tetra-primer amplification refractory mutation system (ARMS) PCR. The Genotypic and allelic assessments were performed using various statistical techniques. Results The AC genotype and C allele of MTHFR A1298C were found to be associated with decreased risk of PE (odds ratio [OR]: 0.31, risk ratio [RR]: 0.58, p = 0.01), and (odds ratio [OR]: 0.49, risk ratio [RR]: 0.61, p = 0.04), respectively. Conclusion In conclusion, genetic polymorphism A1298C in MTHFR may pose a protective effect in the studied population.

MTHFR Polymorphisms and Cardiac Parameters in Patients with Diabetic Retinopathy.

Diabetes Mellitus (DM) is directly associated with cardiovascular dysfunctions and microvascular complications, such as diabetic retinopathy (DR). The association between DR and increased risks of developing cardiovascular diseases has been described. The low activity of the Methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in the metabolism of homocysteine, can lead to hyperhomocysteinemia that has already been related to cardiac outcomes and resistance to insulin. The A1298C and C677T polymorphisms in the MTHFR can reduce enzyme activity. The study aims to analyze the association between MTHFR genotypes and cardiac parameters in patients with DR. DM patients diagnosed with DR (n=65) were categorized and compared according to MTHFR genotypes A1298C (AA and AC+CC groups) and C677T (CC and CT+TT) groups; biochemical, cardiological, anthropometric, genetic, lifestyle and vitamin B9 and B12 consumption variables. Fischer's exact test and Poisson regression were performed to assess the relationship between variables. Comparing echocardiographic and electrocardiogram parameters within genotypic groups, we found a significant association between left atrial dilation and C677T polymorphism. Left atrium diameter was higher in the T allele carriers (CT+TT group), with a prevalence ratio of 0.912. This association was confirmed in the regression model, including confounding variables. The other cardiac structural and functional parameters studied were not significantly associated with the A1298C or C677T genotypes. The MTHFR C677T genotype may contribute to atrial remodeling in RD patients. We found an association between the diameter of the left atrium and the T allele of the MTHFR C677T polymorphism in patients with DR.

Вплив поліморфізма гена рецепторів ангіотензина ii типу 1 на ефективність антигіпертензивної терапії у хворих із гіпертонічною хворобою, які перенесли інфаркт міокарда за результатами довготривалого спостереження

The purpose of the study was to evaluate the effectiveness of antihypertensive therapy based on the data of daily blood pressure monitoring in patients with hypertension and a history of myocardial infarction, taking into account the A1166C polymorphism of the angiotensin II type 1 receptor gene, based on the results of long-term follow-up. Materials and methods. The study included 36 men with arterial hypertension of the 1st to 3rd degree who had suffered a myocardial infarction. The average age was 57.0 (52.0; 64.0) years, the experience of arterial hypertension – 6.3 (4.0; 15.0) years, the period after a myocardial infarction – 48.0 (12.0; 144.0) months. When determining the A1166C polymorphism of the angiotensin II type 1 receptor gene, patients were divided into 3 groups: group 1 consisted of 18 (50%) patients with the AA genotype, group 2 included 12 (33.3%) patients with the AС genotype, and group 3 – 6 (16.7%) patients with СС genotype of angiotensin II type 1 receptor gene. Daily blood pressure monitoring was carried out at the beginning of the study and after 38 months. Results and discussion. At the beginning of the study, based on the results of daily blood pressure monitoring, it was found that in the group as a whole, the levels of systolic blood pressure and diastolic blood pressure, the pressure load index – the diastolic blood pressure time index corresponded to the target values according to the median, but the pressure load indices for systolic blood pressure exceeded the normal range. Against the background of long-term antihypertensive therapy, a reliable decrease in systolic blood pressure levels was established for all time periods of the day, especially during the daytime. A significant decrease in the values of the pressure load indices was established – the time index of systolic blood pressure at daytime (delta -10.49%, which was -27.9%) and the area index of systolic blood pressure at daytime (delta -34.89 mm Hg x h, which was -32.0%) (p &lt;0.05). When analyzing the effectiveness of long-term antihypertensive therapy depending on the A1166C polymorphism of the angiotensin II type 1 receptor gene, it was established that the highest percentage of achieving the target blood pressure level (66.7%) in combination with the normalization of the circadian blood pressure rhythm was determined in patients with the AA genotype of the AGTR1 gene. Among patients with AC genotype, 33.3% reached the target blood pressure levels, but it was not possible to achieve normalization of blood pressure variability and pathological patterns of the circadian rhythm of blood pressure persisted, which are signs of a prognostically unfavorable course of the disease. Among patients with CC genotype of the AGTR1 gene, against the background of long-term treatment, 33.3% achieved the target level of blood pressure, in general, the group normalized the degree of nocturnal decrease in blood pressure, but only a decrease in the levels of systolic blood pressure and diastolic blood pressure during the day in combination with increased values of pressure load indices was observed, which indicates insufficiently effective control of arterial hypertension. Conclusion. During the long-term observation of patients with hypertension and a history of myocardial infarction, an assessment of the effectiveness of antihypertensive therapy was carried out taking into account the A1166C polymorphism of the AGTR1 gene based on the results of daily blood pressure monitoring

Interleukin 12B rs3212227 and rs6887695 single nucleotide polymorphisms are associated with the susceptibility to preeclampsia: Genetic, haplotype and bioinformatics analysis

It is well-known that functional single nucleotide polymorphisms (SNPs) in IL-12B gene might intensely change the protein expression level, or modify its functions, which might result in immune disorders. The association between common IL-12B SNPs with preeclampsia (PE) risk has remained unclear yet. In a case-control study, 253 PE patients and 250 healthy subjects were genotyped for SNPs in IL-12B rs3212227 by PCR-RFLP and in IL-12B rs6887695 by AS-PCR. Novel in-silico analysis were performed to predict the potential functions of these polymorphisms, as well. The rs3212227 variation in IL12B gene showed an association with susceptibility to PE. The AC and CC genotypes and also C allele of this SNP were more frequent in patients. Likewise, they were frequent in early onset and late onset PE. The G allele and GC and CC genotype of rs6887695 SNP correlated negatively with PE development and it shown protective effect on PE risk. In addition, the AG and CC haplotypes of IL-12B were more prevalent in PE patients. Then, IL12B AC haplotype was less frequent in PE compare to healthy pregnant women. In-silico analysis of IL-12B rs3212227 gene polymorphism might not have significant impact on the mRNA structure and transcription of IL-12B. The results of our study revealed a significant relationship between rs3212227A/C and rs6887695G/C polymorphisms in IL-12B gene and the risk of PE in the Iranian population.

Rs3761548 (C/A) and rs5902434 (del/ATT) polymorphisms of Foxp3 gene in Iranian patients with migraine

BackgroundMigraine is a neurovascular disorder; several studies have demonstrated the immune system plays a key role in migraine pathogenesis. The aim of this study was to investigate the association between FOXP3 gene polymorphism and susceptibility to migraine.MethodsIn a case–control study, 55 whole blood samples of patients with migraine and 80 healthy samples were collected. After DNA extraction, genotyping of the rs5902434 (del/ATT) and rs3761548 (C/A) FOXP3 was performed using sequence-specific primers method (PCR-SSP).ResultsThe results of this study showed that there were statistically significant differences between patient and control group in genotype frequencies of rs3761548. In addition, the frequency of heterozygous genotype AC at rs3761548 in patients was found to be significantly higher than controls. We also found no significant differences between cases and controls were found in the allelic and genotype distribution of the rs5902434 (del/ATT) polymorphism. None of the rs5902434 (del/ATT) genotypes showed any significant association with the migraine.ConclusionsAccording to finding of our study, polymorphism rs3761548 in FOXP3 gene were associated with susceptibility to migraine. Further studies with larger sample sizes and different populations in other parts of the world are needed to investigate relationship between this polymorphism on migraine susceptibility.

BOLA Gene Polymorphism and Determination of Disease Severity and Susceptibility: Review

Major histocompatibility complex is the gene complex that exists in all vertebrae like humans (HLA), dogs (DLA), bovine (BLA), ovine (OLA), swine (SLA), and equine (ELA). MHC possesses three regions (I, II, III) that control major specific immune responses and contain variety of genes which influence growth, development, reproduction, odor, and olfaction. Measuring levels of polymorphism of these genes can provide indirect measures of the immunological fitness of populations. As humans and mice, cattle have three MHC gene classes (class I, II, and III). Both BoLA class I and II play a role in antigen presentation, however the function of BoLA class III has been releated with components of the complement system. BoLA class II region is extra separated into class IIa and class IIb. In this gene, the genetic polymorphism of class II α and β genes occurs predominantly in exon 2 encoding the antigen binding site. The BoLa-A locus has 32 serologically defined alleles and minimum four further putative alleles in addition to a high frequency of null alleles. With association allele hold DRB3.2*8 (DRB3*1201) and DRB3.2*16 (DRB3*1501) genes are associated with mastitis susceptibility, and DRB3.2*22 (DRB3*1101), DRB3.2*23 (DRB3*2703) and DRB3.2*24 (DRB3*0101) with mastitis resistance. The A8 specificity and the EIAY sequence are significant markers of resistance, while the serine residue is a marker of susceptibility to dermatophlosis. According to the report 2004, BoLA-DRB3 alleles with the amino acid residues Glu, Arg, and valine (Val) at positions 74, 77, and 78, respectively, give resistance to tumor development by BLV infection. On the other hand, HaeIII CC and HaeIII BC genotypes were actually associated with resistance to FMD in contrast, the HaeIII AA genotype was associated with susceptibility to FMD. Another report on infected Egyptian buffaloes with serotype O FMDV genotype AA for FMD resistance while genotype AC for susceptibility to FMD.

Association analysis of polymorphisms of candidate genes for laying traits in Yangzhou geese

Egg production is an important economic trait in the Chinese goose industry. Due to the low heritability of annual egg production traits in geese, large-scale individual selection based on annual egg production measurements cannot be carried out. Therefore, new selection methods must be applied for large-scale early selections. To screen for effective molecular markers for early Yangzhou geese selection, the genotypes and gene frequencies of mutated loci of five candidate genes related to egg production, MAGI-1, ACSF2, ASTN2, KIAA1462, and ARHGAP21, were detected and analyzed by PCR-direct sequencing.Furthermore, correlation analysis was performed with annual egg mass and body weight at the point of lay and egg weight, and the results were as follows:Magi-1 (Record-106975)was A > G, ACSF2 (Record-106582)was A > C, ASTN2 (Record-111407)was A > T, KIAA1462 (Record-134172)was A > T, and the base of ARHGAP21 (Record-112359) was G > T. At all the five loci above, the Yangzhou geese population followed the Hardy-Weinberg equilibrium (P > 0.05). The results of the association analysis between different genotypes and production performance showed no significant differences in annual egg production, body weight at the point of lay, and egg weight, among different genotypes (P > 0.05) at the mutation loci of MAGI-1 and ASTN2. At the ACSF2 and KIAA1462, the annual egg production of AC was significantly higher than that of AA and CC (P < 0.05), the annual egg production of TT was significantly higher than that of AA (P < 0.05), and there were no significant differences in body weight at the point of lay and egg weight, among the three genotypes (P > 0.05). At ARHGAP21, the body weight at the lay point of the TT genotype was the highest, which was significantly higher than that of GG (P < 0.05); however, there was no significant difference with the heterozygous GT genotype for this trait (P > 0.05). Therefore, Genotype AC at ACSF2 and genotype TT at KIAA1462 could be used as favorable genotypes for egg production, and genotype TT at ARHGAP21 could be used as a favorable genotype for weight in Yangzhou geese.

Association of the risk factor UNC13A with survival and upper motor neuron involvement in amyotrophic lateral sclerosis.

The UNC13A gene is an established susceptibility locus for amyotrophic lateral sclerosis (ALS) and a determinant of shorter survival after disease onset, with up to 33.0 months difference in life expectancy for carriers of the rs12608932 risk genotype. However, its overall effect on other clinical features and ALS phenotypic variability is controversial. Genotype data of the UNC13A rs12608932 SNP (A-major allele; C-minor allele) was obtained from a cohort of 972 ALS patients. Demographic and clinical variables were collected, including cognitive and behavioral profiles, evaluated through the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) - Italian version and the Frontal Behavioral Inventory (FBI); upper and lower motor neuron involvement, assessed by the Penn Upper Motor Neuron Score (PUMNS) and the Lower Motor Neuron Score (LMNS)/Medical Research Council (MRC) scores, respectively; the ALS Functional Rating Scale Revised (ALSFRS-R) score at evaluation and progression rate; age and site of onset; survival. The comparison between the three rs12608932 genotypes (AA, AC, and CC) was performed using the additive, dominant, and recessive genetic models. The rs12608932 minor allele frequency was 0.31 in our ALS cohort, in comparison to 0.33-0.41 reported in other Caucasian ALS populations. Carriers of at least one minor C allele (AC + CC genotypes) had a shorter median survival than patients with the wild-type AA genotype (-11.7 months, p = 0.013), even after adjusting for age and site of onset, C9orf72 mutational status and gender. Patients harboring at least one major A allele (AA + AC genotypes) and particularly those with the wild-type AA genotype showed a significantly higher PUMNS compared to CC carriers (p = 0.015 and padj = 0.037, respectively), thus indicating a more severe upper motor neuron involvement. Our analysis did not detect significant associations with all the other clinical parameters considered. Overall, our findings confirm the role of UNC13A as a determinant of survival in ALS patients and show the association of this locus also with upper motor neuron involvement.

Effect of MTHFR A1298C Gene Polymorphism on Acute Coronary Syndrome.

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Acute coronary syndrome is a manifestation of CVD. In Indonesia, limited studies have been conducted on genetics as a potential risk factor for acute coronary syndrome (ACS). Consequently, this study aimed to examine the effect of the methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism on the incidence of ACS. The study employed a case-control design. Outpatients from the cardiology and internal medicine clinics at the University of Airlangga (UNAIR) Hospital in Surabaya, Indonesia, constituted the study population. The case group comprised 60 patients with a history of ACS, while the control group consisted of 30 patients without a history of cardiovascular complaints. MTHFR A12980C gene polymorphism examination was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR RFLP) method at the Tropical Disease Center UNAIR Laboratory. Among the ACS group, 29 (48.1%), 13 (21.7%), and 18 (30%) of the individuals had AA, AC, and CC genotype patterns, respectively. In the control group, 16 individuals had AA (53.3%), 6 AC (20%), and 8 CC (26.7%). The C allele variant was identified in 41% of the ACS group and 37% of the control group. The odds ratio (OR) for the incidence of ACS was 1.195 (95% confidence interval [CI]; 0.381-3.752), 1.241 (95% CI; 0.481-3.486), and 1.222 (95% CI; 0.381-3.752). Chi-square analysis revealed no association between MTHFR A1298C gene polymorphism and the incidence of ACS (P > 0.05). MTHFR A1298C gene polymorphism did not significantly affect ACS incidence.

Association of ABCC8 gene variants with response to sulfonylurea in type 2 diabetes mellitus.

Diabetes mellitus (DM) is associated with high blood glucose levels and sulfonylureas (SFUs) are one of the treatment options for DM. SFUs bind to sulfonylurea-1 receptor (SUR1), which is encoded by the ABCC8 gene and leads to blood glucose reduction. Genetic variants like rs757110 and rs1799854 of ABCC8 can influence the response to the drug's efficiency. Therefore, this study aimed to investigate the association between the ABCC8 rs757110 and rs1799854 genetic variants and response to SFUs treatment. Totally, 61 DM patients with SFUs treatment were included. Baseline characteristics of the patients were recorded and 5 ml of blood was taken from each patient. After DNA extraction, a sequence containing rs757110 and rs1799854 was synthesized by the PCR method, and the PCR products were used for Sanger sequencing. Frequencies of GG, GA, and AA genotypes of rs1799854 variant was 12 (40%), 14 (46.7%), and 4 (13.3%), and the frequencies of CC, AC, and AA genotypes for rs757110 variant was 3 (9.7%), 5 (16.1%) and 23 (74.2%) in, respectively. Patients with different genotypes had the same age, BMI (body mass index), initial FBS (Fasting blood sugar), initial HbA1c, treatment duration, gender and history of smoking, alcohol consumption, and exercise. There was no significant difference in FBS and HbA1c changes after SFUs treatment between patients with rs757110 variant (p = 0.39 for FBS and p = 0.76 for HbA1c) and rs1799854 (p = 0.24 for FBS and p = 0.36 for HbA1c). The rs1799854 and rs757110 variants of the ABCC8 gene had no significant influence on response to SFUs treatment.

CYP1A2 Genetic Variation, Coffee Intake, and Kidney Dysfunction

Caffeine is detoxified by cytochrome P450 1A2 (CYP1A2), and genetic variation in CYP1A2 impacts the rate of caffeine clearance. Factors that may modify the association between coffee intake and kidney disease remain unclear. To assess whether CYP1A2 genotype modifies the association between coffee intake and kidney dysfunction. The Hypertension and Ambulatory Recording Venetia Study (HARVEST) was a prospective cohort study of individuals with stage 1 hypertension in Italy; HARVEST began on April 1, 1990, and follow-up is ongoing. The current study used data from April 1, 1990, to June 30, 2006, with follow-up of approximately 10 years. Blood pressure and biochemical data were collected monthly during the first 3 months, then every 6 months thereafter. Data were analyzed from January 2019 to March 2019. Participants were screened and recruited from general practice clinics. The present study included 1180 untreated participants aged 18 to 45 years with stage 1 hypertension; those with nephropathy, diabetes, urinary tract infection, and cardiovascular disease were excluded. Coffee intake and CYP1A2 genotype rs762551 were exposures analyzed over a median follow-up of 7.5 (IQR, 3.1-10.9) years. Albuminuria (defined as an albumin level of ≥30 mg/24 h) and hyperfiltration (defined as an estimated glomerular filtration rate of ≥150 mL/min/1.73 m2) were the primary outcomes as indicators of kidney dysfunction. Among 1180 participants, genotyping, lifestyle questionnaires, and urine analysis data were obtained from 604 individuals (438 [72.5%] male) with a mean (SD) age of 33.3 (8.5) years and a mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 25.4 (3.4). A total of 158 participants (26.2%) consumed less than 1 cup of coffee per day, 379 (62.7%) consumed 1 to 3 cups per day, and 67 (11.1%) consumed more than 3 cups per day. Genotype frequencies for rs762551 (260 participants [43.1%] with genotype AA, 247 participants [40.8%] with genotype AC, and 97 participants [16.1%] with genotype CC) did not differ between coffee intake categories. The level of risk of developing albuminuria, hyperfiltration, and hypertension, assessed by Cox regression and survival analyses, was not associated with coffee intake in the entire group or among fast metabolizers. The risks of albuminuria (adjusted hazard ratio [aHR], 2.74; 95% CI, 1.63-4.62; P < .001), hyperfiltration (aHR, 2.11; 95% CI, 1.17-3.80; P = .01), and hypertension (aHR, 2.81; 95% CI, 1.51-5.23; P = .001) increased significantly among slow metabolizers who consumed more than 3 cups per day. In this study, the risks of albuminuria, hyperfiltration, and hypertension increased with heavy coffee intake only among those with the AC and CC genotypes of CYP1A2 at rs762551 associated with slow caffeine metabolism, suggesting that caffeine may play a role in the development of kidney disease in susceptible individuals.

Evaluation of short day local and exotic onion genotypes

Onion is one of the important spices of daily dishes in Bangladesh and are shortage in production of the crop. Due to high photosensitivity in onion, only short-day types are suitable for cultivation in the particular agroclimatic condition of the country. But lack of high yielding potentiality in the existing cultivar along with limited variability within the available germplasm is the major drawback in onion production. To mitigate the problem, the present investigation was done to identify suitable short-day onion genotypes at the Regional Spices Research Centre, BARI, Gazipur during rabi 2018-19 and 2019-20. Twenty-nine local and exotic short-day onions were evaluated including two local checks BARI Piaz-1 and BARI Piaz-4. δ2p and PCV was higher than δ2g and GCV in almost all the traits studied and higher heritability (h2b) was observed for total bulb yield. Significant variations were found in morphological and physiological traits for bulb production. Considerably higher bulb length and diameter were found from Ac_G_18_379, Ac_B_18_413, Ac_B_18_420, Ac_B_18_428, BARI Piaz-4, Ac_B_18_419 and Ac_B_18_417. Minimum bulb splitting (%) and bolting (%) were obtained from the genotypes Ac_G_18_379, Ac_G_18_381, Ac_B_18_413 and BARI Piaz-4. Higher dry matter content was noted for the genotypes BARI Piaz-4 (17.9 %), Ac_B_18_425 (21.73 %) and Ac_G_18_384 (21.57 %) along with the TSS ranged from 10.5 to 17.780Brix. The maximum bulb yield was obtained from the genotype Ac_B_18_413 (20.69 t/ha), followed by Ac_G_18_383 (20.6 t/ha), Ac_B_18_419 (18.48 t/ha) and Ac_B_18_417 (18.2 t/ha). These genotypes could be recommended for commercial cultivation as well as to use in future onion breeding program. Bangladesh J. Agri. 2022, 47(2): 27-43

Association between CDKN1A gene rs1801270 polymorphisms and susceptibility to colorectal cancser in an Iranian population

CDKN1A gene is implicated in cell differentiation, development process, repair, apoptosis, senescence, migration, and tumorigenesis. Somatic alterations and polymorphisms may interfere in the function of CDKN1A, and this could affect the individual susceptibility to colorectal cancer (CRC). Here in, we evaluated the importance of single nucleotide polymorphic variants in codon 31 of CDKN1A (rs1801270: C > A) for the development of colorectal cancer in an Iranian population. A total of 150 CRC patients and 150 healthy controls were enrolled in this study. Genomic DNA was extracted from peripheral blood specimens. Genotypes were determined using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay. In CRC patients, the genotype frequencies detected were 90%, 8.0% and 2.0%2 for CC, AC and AA genotypes while the genotype frequencies in control group were 78%, 20.7% and 1.35% 1.35% for CC, AC and AA genotype, respectively. There were statistically significant differences in the distribution of CDKN1A rs1801270 genotypes and allele frequencies between colorectal cancer patients and healthy controls (p value = 0.021). Also, results indicated a significant negative association between AC genotype and risk of colorectal cancer occurrence. (Odds ratio (OR)=0.357; 95% confidence interval (CI)=0.168–0.760, p = 0.007). Our data suggest that the AC genotype may have a protective role in the development of CRC in an Iranian population.