Allelic and genotype frequencies of major CYP2B6 polymorphisms in the Pakistani population

Coronary artery disease (CAD) is an inflammatory heart disease characterized by the narrowing of coronary arteries. Paraoxonase 3 (PON3) is a candidate gene for protection against CAD development as it reduces oxidative stress and lipid peroxidation. The present study aimed to explore the association of PON3 rs2375003 polymorphism with CAD development and serum lipid levels in the Pakistani population. Study subjects included 300 CAD patients and 300 age and sex matched healthy individuals. The genotyping of rs2375003 polymorphism was done using an allele specific polymerase chain reaction and serum lipid levels were determined. In this study, the genotype frequencies of rs2375003 polymorphismin in CAD patients were TT (2%), CT (8%), CC (90%) as compared to TT (3%), CT (6%), CC (91%) in the healthy subjects. No association was observed between rs2375003 polymorphism and CAD risk (p>0.05). The CT genotype of rs2375003 polymorphism marginally increased the risk for CAD development (OR: 1.36; 95% CI 0.72-2.56) by causing a marginal rise in total cholesterol, low density lipoprotein cholesterol and triglyceride levels, and a marginal drop in high density lipoprotein cholesterol levels. The CT genotype of rs2375003 polymorphism and altered lipid levels might act as potential risk factors in the etiology of CAD in the Pakistani population.

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Effect of the Common Fat Mass and Obesity Associated Gene Variants on Obesity in Pakistani Population: A Case-Control Study

BioMed Research International ◽

10.1155/2015/852920 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Shabana ◽

Shahida Hasnain

Keyword(s):

Fat Mass ◽

Anthropometric Measures ◽

Single Nucleotide ◽

Pakistani Population ◽

Global Epidemic ◽

Asian Populations ◽

Risk Alleles ◽

Genotype Frequencies ◽

Quantitative Manner ◽

Control Study

Background/Objective. Obesity has become a global epidemic due to an increase in the number of obese individuals worldwide. There is little research in the field of obesity genetics in Pakistan. The aim of the current study was to analyze the association of common variants in Fat Mass and Obesity associated(FTO)gene with obesity in Pakistan, to find out the effect of the selected SNPs on anthropometric and biochemical traits, and to observe whether these variants act synergistically.Methods. Samples from 631 subjects were taken after informed consent and were used for serum parameters and genetic analysis. Lipid profile was determined, tetra-ARMS PCR was used for genotyping, and allele/genotype frequencies and genescore were calculated.Results. AllFTOvariants were associated with obesity, and some biochemical and anthropometric measures and had higher minor allele frequencies than those reported for Asian populations previously. The risk allele of each single nucleotide polymorphism resulted in an increase in BMI in a quantitative manner.Conclusion. Common forms of obesity are due to a combined net effect of many variants presented in same or different genes. The more the number of risk alleles present, the higher the risk and severity of obesity resulting from an increase in BMI.

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Association of variable number of tandem repeats (VNTR) and T941G polymorphism of monoamine oxidase (MAO-A) gene with aggression in Pakistani subjects

African Health Sciences ◽

10.4314/ahs.v21i1.24 ◽

2021 ◽

Vol 21 (1) ◽

pp. 180-8

Author(s):

Sumbal Sarwar ◽

Shabana ◽

Shahida Hasnain

Keyword(s):

Monoamine Oxidase ◽

Promoter Region ◽

Tandem Repeats ◽

Variable Number ◽

Monoamine Oxidase A ◽

Pakistani Population ◽

Behavioral Traits ◽

Genotype Frequencies ◽

Pcr Rflp ◽

Mao A

Background: Human behavioral traits are known to be significantly heritable. Certain individuals have a greater tendency of negative behavioral aspects including aggression. The quest to identify tunderlying genetic causes has led to identification of a number of genetic markers, one of them is the monoamine oxidase-A (MAO-A) gene. Objective: We aimed to genotype a variable number of tandem repeats (VNTRs) in the promoter region and a functional SNP within this gene (T941G, dbSNP ID: rs6323) in the recruited cohort of 482 subjects. Methods: After DNA isolation, genotyping was done by PCR-RFLP and the results were confirmed by sequencing. Results: For VNTRs, the results showed, highest frequency of 3.5 repeats in males and 4 repeats in females in the promoter region. The genotype frequencies for the SNP in cases were GG=16.3%, TG=20.6% and TT=63.1%, while in controls, the frequencies were GG=12.7%, TG=6.3%, and TT=81.0%. The allele frequencies were significantly different between cases and controls (p=0.015; OR=1.51; CI=1.085-2.102). Conclusion: The selected VNTR and SNP appeared to be significantly associated with aggression. These VNTRs and SNP have not been studied previously in the Pakistani population, hence they represent a unique ethnic group. These results, however, would have to be replicated in larger cohorts. Keywords: Aggression; MAO-A gene; VNTRs; T941G; rs6323; Pakistan.

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The Leu33/Pro Polymorphism (PIA1/PIA2 ) of the Glycoprotein IIIa (GPIIIa) Receptor Is Not Related to Myocardial Infarction in the ECTIM Study

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656134 ◽

1997 ◽

Vol 77 (06) ◽

pp. 1179-1181 ◽

Cited By ~ 72

Author(s):

Stefan-Martin Herrmann ◽

Odette Poirier ◽

Pedro Marques-Vidal ◽

Alun Evans ◽

Dominique Arveiler ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Coronary Syndromes ◽

Case Control Study ◽

Case Control ◽

Receptor Complex ◽

Genotype Frequencies ◽

Large Multicenter Study ◽

Glycoprotein Iiia ◽

Coronary Syndromes ◽

Control Study

SummaryThe GPIIb/IIIa receptor complex may contribute to acute coronary syndromes by mediating platelet aggregation. The Leu33/Pro polymorphism (PlAl/PlA2) of the GPIIIa has recently been shown to be associated with CHD in a small case-control study. We have investigated this polymorphism in a large multicenter study of patients with myocardial infarction and controls and found no difference in the distribution of allele and genotype frequencies between cases and controls.

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IL-10-592 A/C Gene Polymorphism and Cytokine Levels are Associated with Susceptibility to Drug Resistance in Tuberculosis

Turkish Journal of Immunology ◽

10.25002/tji.2020.1235 ◽

2020 ◽

Vol 8 (3) ◽

pp. 103-112

Author(s):

Atefeh SADEGHI SHERMEH ◽

Majid KHOSHMIRSAFA ◽

Ali-Akbar DELBANDI ◽

Payam TABARSI ◽

Esmaeil MORTAZ ◽

...

Keyword(s):

Serum Levels ◽

World Health ◽

Control Group ◽

Drug Resistant ◽

Nucleotide Polymorphisms ◽

Genotype Frequencies ◽

Cytokine Levels ◽

Ifn Γ ◽

Health Organization ◽

And Function

Introduction: Tuberculosis (TB) and especially resistant forms of it have a substantial economic burden on the community health system for diagnosis and treatment each year. Thus, investigation of this field is a priority for the world health organization (WHO). Cytokines play important roles in the relationship between the immune system and tuberculosis. Genetic variations especially single nucleotide polymorphisms (SNPs) impact cytokine levels and function against TB. Material and Methods: In this research SNPs in IFN-γ (+874 T/A) and IL-10 (-592 A/C) genes, and the effects of these SNPs on cytokine levels in a total of 87 tuberculosis patients and 100 healthy controls (HCs) were studied. TB patients divided into two groups: 1) 67 drug-sensitive (DS-TB) and 2) 20 drug-resistant (DR-TB) according to drug sensitivity test using polymerase chain reaction (PCR). For the genotyping of two SNPs, the PCR-based method was used and IFN-γ and IL-10 levels were measured by ELISA in pulmonary tuberculosis (PTB) and control group. Results: In -592A/C SNP, only two genotypes (AA, AC) were observed and both genotypes showed statistically significant differences between DR-TB and HCs (p=0.011). IL-10 serum levels in PTB patients were higher than HCs (p=0.02). The serum levels of IFN-γ were significantly higher in DS-TB patients than that of the other two groups (p<0.001); however, no significant differences were observed for allele and genotype frequencies in IFN-γ +874. Conclusions: Our results suggest that the SNP at -592 position of IL-10 gene may be associated with the susceptibility to DR-TB. However, further investigation is necessary. Keywords: Polymorphism, IFN-γ, IL-10, tuberculosis, drug-resistant tuberculosis

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Сочетанные генотипы генов, кодирующих белки холецистокининергической системы и ферменты фолатного цикла в значительной степени связаны с мигренью

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/0031-2991.2020.01.5-14 ◽

2020 ◽

Author(s):

J.E. Azimova ◽

E.A. Klimov ◽

E.A. Naumova ◽

Z.G. Kokaeva ◽

A.I. Zaitseva ◽

...

Keyword(s):

Population Control ◽

Statistical Significance ◽

Episodic Migraine ◽

Protective Role ◽

Control Group ◽

Maoa Gene ◽

Specific Pcr ◽

Genotype Frequencies ◽

Biochemical Systems ◽

Combined Genotypes

Перспективным в изучении биомаркеров мигрени может быть многолокусный анализ, в частности, анализ частот сочетанных генотипов. Цель исследования - поиск составных генетических биомаркеров индивидуальной предрасположенности к мигрени, полученных на основе полиморфизмов генов, уже показавших статистическую значимость при однолокусном ассоциативном анализе. Методика. Обследовано 155 пациентов с мигренью (104 пациента с эпизодической мигренью, 51 - с хронической мигренью), наблюдавшихся в Университетской клинике головной боли (Москва). Все пациенты - представители белой расы, жители Московского региона. Возраст пациентов - 30-50 лет. Контроль составили 365 необследованных лиц (популяционный контроль). Выявление исследуемых 22 генов (всего 31 SNP) осуществляли методом ПЦР, ПЦР-ПДРФ, аллель-специфичной ПЦР и ПЦР в реальном времени. Выявление ассоциированных с мигренью сочетанных генотипов проводили с использованием программы анализа полигенных данных APSampler v3.6. Результаты. Выявлено 8 сочетанных генотипов с высокой статистически значимой ассоциацией с мигренью (ОШ>20,0). В состав сочетанных генотипов вошли гены: CCKAR, CCKBR, COMT, MTHFR, MTR, MTRR. Так же выявлено 4 защитных сочетанных генотипа (ОШ<0,02), основным в которых является ген MAOA. Заключение. Полученные данные об ассоциированных с мигренью сочетанных генотипах указывают на значимую роль в патогенезе заболевания 2 биохимических систем: 1) холецистокининергической системы, регулирующей выброс и обратный захват дофамина, и 2) фолатного цикла, в ходе работы которого гомоцистеин метаболизируется в метионин. Результаты, полученные в данном исследовании, позволяют говорить о защитной роли аллеля VNT:R4 гена MAOA.Multilocus analysis, specifically, analysis of combined genotype frequencies may be promising in studying migraine biomarkers. The aim of the study was to search for composite genetic biomarkers, which would predict individual predisposition to migraine, obtained on the basis of gene polymorphisms that have already shown a statistical significance in a single-locus associative analysis. Methods. 155 patients with migraine aging 41.7 ± 12.5 who had been followed up at the University Clinic of Headache, Moscow, were evaluated (104 patients with episodic migraine and 51 with chronic migraine). All patients were white and residents of the Moscow region. The control group included 365 unexamined individuals (population control). Identification of The 22 genes under study (total, 31 SNPs) were identified by PCR, PCR-RFLP, allele-specific PCR, and real-time PCR. Combined genotypes associated with migraine were identified using the APSampler v3.6 software for polygenic data analysis. Results. Eight combined genotypes were identified with a highly significant association with migraine (OR> 20.0). The combined genotypes included the CCKAR, CCKBR, COMT, MTHFR, MTR, and MTRR genes. Four protective combined genotypes were also identified (OS <0.02) with the MAOA gene as the major one. Conclusion. Our data on migraine-associated combined genotypes indicate a significant role in the migraine pathogenesis of two biochemical systems, i) the cholecystokininergic system that regulates the release and reuptake of dopamine, and ii) the folate cycle, where homocysteine is metabolized to methionine. The results obtained in this study suggest a protective role of the VNT: R4 allele of the MAOA gene.

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IDENTIFYING THE C677T POLYMORPHISM OF MTHFR GENE BY PCR-RFLP TECHNIQUE

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2011.2.3 ◽

2011 ◽

pp. 28-35

Author(s):

Keyword(s):

Internal Control ◽

Restriction Site ◽

Mthfr Gene ◽

C677t Polymorphism ◽

Mthfr Genotype ◽

Restriction Digest ◽

Genotype Frequencies ◽

Pcr Rflp ◽

Sequencing Technique ◽

Volunteer Group

Background: The C677T polymorphism of MTHFR gene is a risk factor of many diseases. This study is aimed at: (1) Improving a PCR-RFLP process with the own designed primers to identify the C677T polymorphism of MTHFR gene. (2) Evaluating the prevalence of the C677T polymorphism of MTHFR gene in volunteer group. Materials and method: DNA samples was extracted from peripheral blood of 60 volunteers. Designing primers by using FastPCR software, then improving PCR technique. Standardizing the optimal conditions of restriction digest by HinfI. Confirming the results of polymorphism by DNA sequencing technique. Results: We designed successfully primers to amplify fragment of MTHFR gene including C677T polymorphism and an obligatory restriction site of HinfI (as internal control). 0.5 µl of HinfI enzyme (10 U/µl) is enough for restriction digest. The MTHFR genotype frequencies were: 71.67 % (677CC); 25% (677CT); and 3.33 % (677TT). Conclusion: We standardized successfully PCR-RFLP technique to identifying C677T polymorphism of MTHFR gene. Keywords: C677T polymorphism, MTHFR gene, PCR-RFLP

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Identification of Functional Variants Associated with Obesity in Pakistani Kindred

Current Chinese Science ◽

10.2174/2210298101666200909160022 ◽

2020 ◽

Vol 1 (1) ◽

pp. 58-68

Author(s):

Ayesha Aftab ◽

Syed Babar Jamal ◽

Syeda Marriam Bakhtiar

Keyword(s):

Functional Analysis ◽

Protein Stability ◽

Treatment Strategies ◽

Type Ii Diabetes Mellitus ◽

Diagnosis And Treatment ◽

Ratio Test ◽

Processed Food ◽

Pakistani Population ◽

Functional Variants ◽

Environmental Causes

Background: Obesity is an emerging pandemic considered to be an outcome of change in lifestyle owing to more processed food and the use of mechanical locomotives. Obesity has not only appeared as a problem in the esthetic appearance of an individual rather is a serious health issue due to its associations with various chronic diseases such as coronary and cardiovascular problems, hypertension, osteoarthritis, type-II diabetes mellitus, hyperlipidemia, and certain cancers. It is estimated that 30 percent of the world’s population, i.e. approximately 2.1 billion people, are victims of obesity. In addition to environmental causes, various genes and a group of genes are reported to be increasing the suceptibility of obesity. Objective: Pakistan is a heterogeneous population, an amalgam of various races, therefore, narrowing down the list of obesity-associated genes and their functional variance could help molecular biologists to select potential SNPs in the Pakistani population for molecular diagnosis and treatment. Method: The extraction of a set of obesity-associated genes has been performed by using Polysearch2. SNPs for each gene are retrieved from dbSNP. RegulomeDB and SNPinfo tools have been used for the functional analysis of SNPs retrieved against the Pakistani population. For the prediction of potential deleterious SNPs, SIFT, Polyphen-2, MUTTASTER, MUTASSESSOR, and LRT (likelihood ratio test) are utilized. Functional analysis of potential deleterious SNPs has been performed by studying protein stability and mapping of identified SNPs to protein structure. For the protein stability analysis, I-Mutant and SNPs3D have been used. Results: Four genes FTO, POMC, LEPR, and MC4R and further analysis revealed 3 deleterious SNPs in FTO, 4 in POMC, 1 in LEPR, and 1 in MC4R. Conclusion: This research was designed to identify obesity-associated genes and the most impactful deleterious SNPs in these genes. These findings will be helpful for the molecular biologists and pharmacists to design better and focused diagnosis and treatment strategies.

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AB0008 THE IMPACT OF STAT4 RS7574865, IL6 RS1800795, IL6R RS2228145 AND RS4845618 ON RHEUMATOID ARTHRITIS SUSCEPTIBILITY IN BELARUSIAN POPULATION

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1990 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1307.1-1308

Author(s):

E. Siniauskaya ◽

T. Kuzhir ◽

V. Yagur ◽

R. Goncharova

Keyword(s):

Rheumatoid Arthritis ◽

Blood Donors ◽

Genetic Model ◽

Online Tool ◽

Genotype Frequencies ◽

Systemic Disorder ◽

Autoimmune Pathogenesis ◽

The Impact ◽

Arthritis Susceptibility

Background:Rheumatoid arthritis (RA) is a chronic systemic disorder of the connective tissue of still unknown aetiology and complex autoimmune pathogenesis that primarily affects small joints. HLA alleles provide for 11-37% of the RA heritability, suggesting the substantial role of the non-HLA loci in genetic predisposition to RA. Among non-HLA loci,IL6, IL6RandSTAT4genes attract attention, however, the data concerning their influence on RA risk are somewhat contradictory.Objectives:The aim of the study was to analyze the involvement of four SNPs (STAT4rs7574865,IL6rs1800795,IL6Rrs2228145 and rs4845618) in RA susceptibility.Methods:187 patients diagnosed with RA (mean age 58.2 ± 11.9), and 380 healthy blood donors (mean age 37.18 ± 10.69 years) were included into the study. DNA extraction from peripheral blood samples was performed using the phenol-chloroform method. SNPs were genotyped using the real-time PCR with fluorescent probes. The allele and genotype frequencies were compared using the χ2 test. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using the VassarStats online tool.Results:Utilizing recessive genetic model we found an association between TT genotype ofSTAT4rs7574865 (OR = 2.362; 95%CI [1.0378 – 5.376], p = 0.038) and RA. ForIL6rs1800795, it was found that CC genotype had significantly higher frequency among patients with rheumatoid arthritis as compared to that in controls (OR = 1.52; 95%CI [1.02 – 2.27], p = 0.0456). No associations ofIL6Rrs2228145 and rs4845618 SNPs with risk of RA were found in the total group of patients vs. controls. It was also shown thatIL6rs1800795 CC genotype frequency was significantly higher among the patients with RF-negative status (p = 0.0019).Conclusion:Thus, we provide evidence for association of theSTAT4rs7574865 andIL6rs1800795 variants with risk of RA in the Belarusian population, some features of interplay being revealed between gene polymorphisms analyzed and RA antibody status. Abovementioned SNPs may contribute to RA genetic susceptibility in the Belarusian population.Disclosure of Interests:None declared

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Five genetic polymorphisms of cytochrome P450 enzymes in the Czech non-Roma and Czech Roma population samples

Drug Metabolism and Personalized Therapy ◽

10.1515/dmdi-2020-0103 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Lucie Dlouhá ◽

Věra Adámková ◽

Lenka Šedová ◽

Věra Olišarová ◽

Jaroslav A. Hubáček ◽

...

Keyword(s):

Cytochrome P450 ◽

Genetic Polymorphisms ◽

Metabolic Pathways ◽

Cytochromes P450 ◽

Taqman Assay ◽

Cytochrome P450 Enzymes ◽

Roma Population ◽

Czech Population ◽

Genotype Frequencies ◽

Pcr Rflp

AbstractObjectivesCytochromes P450 play a role in human drugs metabolic pathways and their genes are among the most variable in humans. The aim of this study was to analyze genotype frequencies of five common polymorphisms of cytochromes P450 in Roma/Gypsy and Czech (non-Roma) population samples with Czech origin.MethodsRoma/Gypsy (n=302) and Czech subjects (n=298) were genotyped for CYP1A2 (rs762551), CYP2A6 (rs4105144), CYP2B6 (rs3745274) and CYP2D6 (rs3892097; rs1065852) polymorphisms using PCR-RFLP or Taqman assay.ResultsWe found significant allelic/genotype differences between ethnics in three genes. For rs3745274 polymorphism, there was increased frequency of T allele carriers in Roma in comparison with Czech population (53.1 vs. 43.7%; p=0.02). For rs4105144 (CYP2A6) there was higher frequency of T allele carriers in Roma in comparison with Czech population (68.7 vs. 49.8%; p<0.0001). For rs3892097 (CYP2D6) there was more carriers of the A allele between Roma in comparison with Czech population (39.2 vs. 38.2%; p=0.048). Genotype/allelic frequencies of CYP2D6 (rs1065852) and CYP1A2 (rs762551) variants did not significantly differ between the ethnics.ConclusionsThere were significant differences in allelic/genotype frequencies of some, but not all cytochromes P450 polymorphisms between the Czech Roma/Gypsies and Czech non-Roma subjects.

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