scholarly journals Inter-ethnic genetic variations and novel variant identification in the partial sequences of CYP2B6 gene in Pakistani population

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11149
Author(s):  
Sagheer Ahmed ◽  
Hizbullah Khan ◽  
Asifullah Khan ◽  
Muhammad Hanif Bangash ◽  
Abrar Hussain ◽  
...  
Keyword(s):  
Ethnic Groups ◽  
Genetic Variance ◽  
Strong Association ◽  
Hypervariable Region ◽  
Nucleotide Polymorphisms ◽  
Pakistani Population ◽  
Splicing Pattern ◽  
Novel Variant ◽  
Cyp2b6 Gene ◽  
Novel Snp

Background Some single nucleotide polymorphisms (SNPs) in the cytochrome P450 (CYP)2B6 gene lead to decreased enzyme activity and have an impact on drug metabolism. The present study was designed to investigate the patterns of genetic distinction across a hypervariable region of the CYP2B6 gene, known to contain important SNPs, i.e. rs4803419 and rs3745274, among five major ethnic groups of the Pakistani population. Methods Arlequin v3.5.DnaSPv6.12. and network 5 resources were used to analyze population genetic variance in the partial CYP2B6 gene sequences obtained from 104 human samples belonging to Punjabi, Pathan, Sindhi, Seraiki and Baloch ethnicities of Pakistan. The partial CYP2B6 gene region analyzed in the current study is previously known to possess important SNPs. Results The data analyses revealed that genetic variance among samples mainly came from differentiation within the ethnic groups. However, significant genetic variation was also found among the various ethnic groups. The high pairwise Fst genetic distinction was observed between Seraiki and Sindhi ethnic groups (Fst = 0.13392, P-value = 0.026) as well as between Seraiki and Balochi groups (Fst = 0.04303, P-value = −0.0030). However, the degree of genetic distinction was low between Pathan and Punjabi ethnic groups. Some SNPs, including rs3745274 and rs4803419, which are previously shown in strong association with increased plasma Efavirenz level, were found in high frequency. Besides, a novel SNP, which was not found in dbSNP and Ensemble databases, was identified in the Balochi ethnicity. This novel SNP is predicted to affect the CYP2B6 splicing pattern. Conclusion These results may have significant implications in Pakistani ethnicities in the context of drugs metabolized by CYP2B6, especially in Seraiki and Balochi ethnicity. The novel heterogeneous SNP, found in the present study, might lead to altered drug-metabolizing potential of CYP2B6 and, therefore, may be implicated in non-responder phenomenon.

The SNP rs560426 Within ABCA4-ARHGAP29 Locus and the Risk of Nonsyndromic Oral Clefts

2020 ◽  
Vol 57 (6) ◽  
pp. 671-677 ◽  
Author(s):  
Yah-Huei Wu-Chou ◽  
Kuo-Ting Philip Chen ◽  
Yi-Chieh Lu ◽  
Yin-Ting Lin ◽  
Hsien-Fang Chang ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Strong Association ◽  
Nucleotide Polymorphisms ◽  
Test Analysis ◽  
Oral Clefts ◽  
The Family ◽  
Abca4 Gene ◽  
Family Based ◽  
New Evidence

Objective: Nonsyndromic oral clefts are common birth defect with complex etiology. In the present study, we attempt to further validate the possible role for ABCA4 and ARHGAP29 in the susceptibility to nonsyndromic oral clefts. Design: We performed allelic transmission disequilibrium test analysis, on 10 eligible single nucleotide polymorphisms (SNPs) and SNP haplotypes using the Family-Based Association Test. Participants: The study sample consisted of 334 case–parent trios of nonsyndromic oral clefts from Taiwanese population, separated into nonsyndromic cleft lip with or without cleft palate (NSCL/P) and nonsyndromic cleft palate only (NSCPO) groups. Results: We found only the SNP rs560426 within the ABCA4 gene showed strong association with NSCPO ( P = .03498; Permuted P = .05382). No association between other 9 selected SNPs in ABCA4-ARHGAP29 region and the risk of nonsyndromic oral clefts was found. For the haplotype analyses, we found only haplotype T-C (rs570926 and rs3789431) in ABCA4 block 2 showed significant association with nonsyndromic NSCL/P in these Taiwanese trios. Conclusions: We used a family-based analysis in 334 Taiwanese case–parent trios to validate the possible role for ABCA4 and ARHGAP29 in the susceptibility to nonsyndromic oral clefts. This study provides a new evidence for an association between the intron variant rs560426 within ABCA4 and nonsyndromic cleft palate which may contribute their regulatory role in craniofacial development.

scholarly journals Novel polymorphisms in TICAM2 and NOD1 associated with tuberculosis progression phenotypes in Ethiopian populations

2018 ◽  
Vol 3 ◽  
Author(s):  
E. Mekonnen ◽  
E. Bekele ◽  
C. M. Stein
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Genetic Variation ◽  
Ethnic Groups ◽  
Human Genetic Variation ◽  
Genetic Associations ◽  
Association Tests ◽  
Phenotype Definition ◽  
Sufficient Cause ◽  
Novel Variant ◽  
Novel Associations

BackgroundInfection by Mycobacterium tuberculosis (Mtb) is a necessary but not sufficient cause for tuberculosis (TB). Although numerous studies suggest human genetic variation may influence TB pathogenesis, there is a conspicuous lack of replication, likely due to imprecise phenotype definition. We aimed to replicate novel findings from a Ugandan cohort in Ethiopian populations.MethodWe ascertained TB cases and household controls (n = 292) from three different ethnic groups. Latent Mtb infection was determined using Quantiferon to develop reliable TB progression phenotypes. We sequenced exonic regions of TICAM2 and NOD1.ResultSignificant novel associations were observed between two variants in NOD1 and TB: rs751770147 [unadjusted p = 7.28 × 10−5] and chr7:30477156(T), a novel variant, [unadjusted p = 1.04 × 10−4]. Two SNPs in TICAM2 were nominally associated with TB, including rs2288384 [unadjusted p = 0.003]. Haplotype-based association tests supported the SNP-based results.ConclusionWe replicated the association of TICAM2 and NOD1 with TB and identified novel genetic associations with TB in Ethiopian populations.

The association of FKBP5 polymorphism with asthma susceptibility in asthmatic patients

2021 ◽  
Vol 32 (4) ◽  
pp. 479-484
Author(s):  
Sura F. Alsaffar ◽  
Haider A. Rasheed ◽  
Jabbar H. Yenzeel ◽  
Haider F. Ghazi
Keyword(s):  
Allele Frequency ◽  
Risk Allele ◽  
Inhaled Corticosteroids ◽  
Control Group ◽  
The Novel ◽  
Nucleotide Polymorphisms ◽  
Asthmatic Patients ◽  
Asthma Susceptibility ◽  
Group Members ◽  
Novel Snp

Abstract Objectives Inhaled corticosteroids are the most effective controllers of asthma, although asthmatics vary in their response. FKBP51 is a major component of the glucocorticoid receptor which regulates its responses to corticosteroids. Therefore, the present study aims to identify the role of FKBP5 gene polymorphism in asthma susceptibility and corticosteroid resistance. Methods DNA was extracted from the blood of 68 asthmatic and 40 control subjects. FKBP5 gene fragments were amplified by PCR and sequenced by the Sanger method. The sequencing results were aligned by mapping on the reference sequences of National center of Biotechnology Information (NCBI) and single nucleotide polymorphisms (SNPs) which were checked. Finally, the genotype, allele frequency and odds ratio (OR) were calculated. Results The FKBP5 fragment sequencing revealed the presence of rs1360780 and one novel SNP found in 17 samples taken from asthmatic patients as compared to db SNP data in the NCBI database. The FKBP5 variant (rs1360780) indicated that the allele frequency of risk allele T was 41.18% in patients and 20% in control group members p<0.001 and OR=2.8 when compared to a wild C allele frequency of 58.82% in patients and 64% in the control group members. The novel SNP FKBP5 was compared to the SNP database in the NCBI database in which wild T allele was substituted with G. The novel SNP was submitted to the ClinVar Submission Portal at NCBI with accession number: rs1581842283 and confirmed an asthma susceptibility risk factor with allele G frequency of 11.76% in asthmatics and 2.5% in the control group members (OR=5.2, p<0.05), as compared to a wild T allele frequency of 88.24% in asthmatics and 97.5% in the control group members. Conclusions The risk allele T of rs1360780 and the novel SNP rs1581842283 risk allele G predict asthma susceptibility but show no association with corticosteroid resistant.

scholarly journals Genetic association study of prolylcarboxypeptidase polymorphisms with susceptibility to essential hypertension in the Yi minority of China: A case–control study based on an isolated population

2020 ◽  
Vol 21 (2) ◽  
pp. 147032032091958 ◽  
Author(s):  
Yanrui Wu ◽  
Hongju Yang ◽  
Chunjie Xiao
Keyword(s):  
Essential Hypertension ◽  
Case Control Study ◽  
Strong Association ◽  
Case Control ◽  
Negative Regulator ◽  
Mountainous Area ◽  
Nucleotide Polymorphisms ◽  
Kinin System ◽  
Kallikrein Kinin System ◽  
Control Study

Objective: Prolylcarboxypeptidase (PRCP) is a negative regulator of the pressor actions of the renin–angiotensin–aldosterone system. It is also involved in the kallikrein–kinin system. This gene has an important role in blood pressure (BP) regulation. Methods: A case–control study was performed for 615 Yi participants (303 cases and 312 controls) from a remote mountainous area in Yunnan Province of China. For the PRCP gene, 11 tag single-nucleotide polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Results: The PRCP gene rs12290550 was associated with the occurrence of essential hypertension (EH) and BP traits. Logistic regression analysis indicated that the rs12290550 T allele was significantly linked to the risk of EH (odds ratio (OR) = 1.85, 95% confidence interval (CI) 1.44–2.39, p = 0.2 × 10−5). Under Bonferroni correction, the H7 TAGCACTAACA haplotype containing the risk allele rs12290550 T increased the risk of EH (OR = 4.53, 95% CI 2.29–8.93, p = 0.2×10−5). Conclusions: The findings of this study demonstrate the strong association of the PRCP gene with EH. rs12290550 may be a useful genetic predictor of EH in the Yi minority.

scholarly journals Estimating the Genetic Variance of Major Depressive Disorder Due to All Single Nucleotide Polymorphisms

2012 ◽  
Vol 72 (8) ◽  
pp. 707-709 ◽  
Author(s):  
Gitta H. Lubke ◽  
Jouke Jan Hottenga ◽  
Raymond Walters ◽  
Charles Laurin ◽  
Eco J.C. de Geus ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Single Nucleotide Polymorphisms ◽  
Depressive Disorder ◽  
Genetic Variance ◽  
Nucleotide Polymorphisms ◽  
Major Depressive ◽  
Single Nucleotide

scholarly journals Identification of somatostatin receptor type 5 gene polymorphisms associated with acromegaly

2011 ◽  
Vol 165 (4) ◽  
pp. 517-525 ◽  
Author(s):  
Darja Ciganoka ◽  
Inga Balcere ◽  
Ivo Kapa ◽  
Raitis Peculis ◽  
Andra Valtere ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Somatostatin Receptor ◽  
Strong Association ◽  
Upstream Region ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Additional Group ◽  
Unstandardized Regression Coefficient ◽  
Design And Methods

ObjectiveThe aim of this study was to characterize the genetic variance of somatostatin receptor 5 (SSTR5) and investigate the possible correlation of such variants with acromegaly risk and different disease characteristics.Design and methodsThe SSTR5 gene coding region and 2000 bp upstream region was sequenced in 48 patients with acromegaly and 96 control subjects. Further, three single nucleotide polymorphisms (SNPs) were analyzed in the same group of acromegaly patients and in an additional group of 475 age- and sex-matched controls.ResultsIn total, 19 SNPs were identified in the SSTR5 gene locus by direct sequencing. Three SNPs (rs34037914, rs169068, and rs642249) were significantly associated with the presence of acromegaly using the initial controls. The allele frequencies were significantly (P<0.01) different between the acromegaly patients and the additional large control group. rs34037914 and rs642249 remained significantly associated with acromegaly after Bonferroni correction and permutation tests (odds ratio (OR)=3.38; 95% confidence interval (CI), 1.78–6.42; P=0.00016 and OR=2.41; 95% CI, 1.41–4.13; P=0.0014 respectively). Haplotype reconstruction revealed two possible risk haplotypes determined by rs34037914 (633T) and rs642249 (1044A) alleles. Both haplotypes were found in significantly higher frequency in acromegaly patients compared with controls (P<0.001). In addition, the 663T allele was significantly associated with a younger age of acromegaly diagnosis (unstandardized regression coefficient β=−10.4; P=0.002), increased body mass index (β=4.1; P=0.004), higher number of adenoma resection (P<0.001) and lack of observable tumor shrinkage after somatostatin analog treatment (P=0.014).ConclusionsOur results demonstrate a previously undetected strong association of two SSTR5 SNPs with acromegaly. The data also suggest a possible involvement of SSTR5 variants in decreased suppression of GH production and increased tumor proliferation.

scholarly journals Applicability of Obesity-Related SNPs and Their Effect Size Measures Defined on Populations with European Ancestry for Genetic Risk Estimation among Roma

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 516 ◽  
Author(s):  
Erand Llanaj ◽  
Péter Pikó ◽  
Károly Nagy ◽  
Gábor Rácz ◽  
Sándor János ◽  
...  
Keyword(s):  
Effect Size ◽  
Genetic Risk ◽  
Association Studies ◽  
Strong Association ◽  
European Ancestry ◽  
Risk Scores ◽  
Nucleotide Polymorphisms ◽  
Continuous Variables ◽  
Roma Population ◽  
The Impact

Investigations on the impact of genetic factors on the development of obesity have been limited regarding the Roma population—the largest and most vulnerable ethnic minority in Europe of Asian origin. Genetic variants identified from genetic association studies are primarily from European populations. With that in mind, we investigated the applicability of data on selected obesity-related single nucleotide polymorphisms (SNPs), obtained from the Hungarian general (HG) population of European origin, on the Hungarian Roma (HR) population. Twenty preselected SNPs in susceptible alleles, known to be significantly associated with obesity-related phenotypes, were used to estimate the effect of these SNPs on body mass index (BMI) and waist circumference (WC) in HG (N = 1783) and HR (N = 1225) populations. Single SNP associations were tested using linear and logistic regression models, adjusted for known covariates. Out of 20 SNPs, four located in FTO (rs1121980, rs1558902, rs9939609, and rs9941349) showed strong association with BMI and WC as continuous variables in both samples. Computations based on Adult Treatment Panel III (ATPIII) and the International Diabetes Federation’s (IDF) European and Asian criteria showed rs9941349 in FTO to be associated only with WC among both populations, and two SNPs (rs2867125, rs6548238) in TMEM18 associated with WC only in HG population. A substantial difference (both in direction and effect size) was observed only in the case of rs1801282 in PPARγ on WC as a continuous outcome. Findings suggest that genetic risk scores based on counting SNPs with relatively high effect sizes, defined based on populations with European ancestry, can sufficiently allow estimation of genetic susceptibility for Roma. Further studies are needed to clarify the role of SNP(s) with protective effect(s).

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