Identification of somatostatin receptor type 5 gene polymorphisms associated with acromegaly

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.

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Multiple Gene Polymorphisms Associated with Exfoliation Syndrome in the Uygur Population

Journal of Ophthalmology ◽

10.1155/2019/9687823 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Yi-Nu Ma ◽

Ting-Yu Xie ◽

Xue-Yi Chen

Keyword(s):

Protective Factor ◽

Lysyl Oxidase ◽

Direct Sequencing ◽

Control Group ◽

Exfoliation Syndrome ◽

Nucleotide Polymorphisms ◽

Age And Gender ◽

Protective Allele ◽

Significant Difference ◽

And Gender

Background. Our previous data suggested that three single-nucleotide polymorphisms (SNPs), rs1048661, rs3825942, and rs2165241, of the lysyl oxidase-like 1 gene (LOXL1) are significantly associated with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG). The following study investigated other SNPs that potentially effect XFS/XFG. Methods. A total of 216 Uygur patients diagnosed with XFS/XFG, and 297 Uygur volunteers were admitted to the First Affiliated Hospital at Xinjiang Medical University between January 2015 and October 2017. Blood samples were collected by venipuncture. Alleles and genotypes of LOXL1, TBC1D21, ATXN2, APOE, CLU, AFAP1, TXNRD2, CACNA1A, ABCA1, GAS7, and CNTNAP2 were analyzed by direct sequencing. Results. The allele G of rs41435250 of LOXL1 was a risk allele for XFS/XFG (P<0.001), whereas the allele G of rs893818 of LOXL1 was a protective allele for XFS/XFG (P<0.001). After adjusting all data for age and gender, the following results were obtained: the frequency of genotype CC for rs7137828 of ATXN2 was significantly higher in XFS/XFG patients than in controls (P=0.027), while no significance was found with reference to the frequency of genotype TT. The frequency of genotype GG for rs893818 of LOXL1 (P<0.001) and the frequency of genotype AA were both significantly higher in XFS/XFG groups compared to the control group (P<0.001). In addition, the frequency of genotype TT for rs41435250 of LOXL1 was higher in XFS/XFG patients than in controls (P=0.003), while no significant difference was found with reference to the frequency of genotype GG after adjusting for age and gender. In addition, the haplotypes G-A/T-G/G-G for rs41435250 and rs893818 were significantly associated with XFS/G. Conclusions. With reference to LOXL1, the rs41435250 resulted as a risk factor and rs893818 as a protective factor for XFS/XFG in the Uygur populations. Meanwhile, the rs16958445 of TBC1D21 and the rs7137828 of ATXN2 have also shown to be associated with pathogenesis of XFS/XFG.

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Association Analysis of Single Nucleotide Polymorphisms in the 5′ Regulatory Region of the IL-6 Gene with Eimeria tenella Resistance in Jinghai Yellow Chickens

Genes ◽

10.3390/genes10110890 ◽

2019 ◽

Vol 10 (11) ◽

pp. 890 ◽

Cited By ~ 1

Author(s):

Hailiang Yu ◽

Wenbin Zou ◽

Shijie Xin ◽

Xiaohui Wang ◽

Changhao Mi ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Association Analysis ◽

Direct Sequencing ◽

Regulatory Region ◽

Eimeria Tenella ◽

Least Square ◽

Bursa Of Fabricius ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

Interleukin 6 (IL-6) is an immunoregulatory cytokine involved in various inflammatory and immune responses. To investigate the effects of single nucleotide polymorphisms (SNPs) and haplotypes of IL-6 on resistance to Eimeria tenella (E. tenella), SNPs in the 5′ regulatory region of IL-6 were detected with direct sequencing, and the effects of SNPs and haplotypes on resistance to E. tenella were analyzed by the least square model in Jinghai yellow chickens. Nineteen SNPs were identified in the 5′ regulation region of IL-6, among which three SNPs were newly discovered. The SNP association analysis results showed that nine of the SNPs were significantly associated with E. tenella resistance indexes; the A-483G locus was significantly associated with the GSH-Px, IL-2, and IL-17 indexes (p < 0.05); the C-447G locus was significantly associated with the SOD, GSH-Px, IL-17, and IL-2 indexes (p < 0.05); and the G-357A locus had significant effects on the CAT and IL-16 indexes (p < 0.05). Haplotype analysis showed that H2H3 and H2H5 were favorable haplotype combinations with good coccidium resistance. Furthermore, we used qRT-PCR and observed that the expression of IL-6 in the infection group was higher than that in the control group in the liver, proventriculus, small intestine, thymus, kidney, and bursa of Fabricius and extremely significantly different than that in the cecum especially (p < 0.01). In summary, SNPs and haplotypes in the 5′ regulatory region of IL-6 have important effects on E. tenella resistance, and the results will provide a reference for molecular marker selection of E. tenella resistance in Jinghai yellow chickens.

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Correlation between miRNA target site polymorphisms in the 3′ UTR of AVPR1A and the risk of hypertension in the Chinese Han population

Bioscience Reports ◽

10.1042/bsr20182232 ◽

2019 ◽

Vol 39 (5) ◽

Cited By ~ 1

Author(s):

Liuping Zhang ◽

Jinwei Liu ◽

Peng Cheng ◽

Fangchao Lv

Keyword(s):

Single Nucleotide Polymorphisms ◽

Mirna Target ◽

Direct Sequencing ◽

Chinese Han Population ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Single Nucleotide ◽

Han Population ◽

Increased Risk

Abstract We aimed to study the relationship between rs11174811 and rs3803107 single nucleotide polymorphisms (SNPs) in miRNA target sites of the 3′ UTR in the arginine vasopressin receptor 1a gene (AVPR1A) and the risk of hypertension in the Chinese Han population. The genotypes at rs11174811 and rs3803107 were analyzed by direct sequencing in 425 Chinese Han patients with hypertension and 425 healthy subjects. AVPR1A expression was investigated by transfecting miR-526b, miR-375, and miR-186 mimics into human umbilical vein endothelial cells (HUVECs) containing AVPR1A rs11174811 CC, CA/AA and AVPR1A rs3803107 GG, GA/AA genotypes. The A alleles of rs11174811 (adjusted OR = 1.424, 95% CI: 1.231–1.599, P<0.001) and rs3803107 (adjusted OR = 1.222, 95% CI: 1.092–1.355; P=0.001) were high risk factors for hypertension. Plasma levels of miR-526b, miR-375, and miR-186 were higher in the study group than in the control group (P<0.001). The expression levels of AVPR1A mRNA in AVPR1A rs11174811 and rs3803107 mutant HUVECs were higher than those in wild-type cells (t = 8.811, 4.068 and P=0.001, 0.015, respectively). The single nucleotide polymorphisms rs11174811 and rs3803107 in the AVPR1A gene are associated with an increased risk of hypertension in the Chinese Han population. This may be related to the effect of these variants on the regulation of AVPR1A expression by miRNAs.

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Interleukin 18 gene promoter polymorphisms in Latvian patients with rheumatoid arthritis

Proceedings of the Latvian Academy of Sciences Section B Natural Exact and Applied Sciences ◽

10.2478/v10046-011-0011-7 ◽

2011 ◽

Vol 65 (1-2) ◽

pp. 1-6

Author(s):

Anna Mihailova ◽

Helena Mikažāne ◽

Jānis Kloviņs ◽

Liene Ņikitina-Zaķe

Keyword(s):

Rheumatoid Arthritis ◽

Direct Sequencing ◽

Gene Promoter ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Interleukin 18 ◽

Promoter Polymorphisms ◽

Phenotypic Data ◽

Genome Database ◽

American College Of Rheumatology

Interleukin 18 gene promoter polymorphisms in Latvian patients with rheumatoid arthritis Interleukin 18 (IL-18) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis (RA). There are controversial reports suggesting that IL-18 promoter polymorphisms may be an independent marker of RA susceptibility. The aim of the present study was to determine whether polymorphisms of the IL-18 gene promoter in positions -607 (rs 1946519) and -656 (rs 1946518) are associated with RA, and its characteristics in the Latvian population. We examined 105 patients with RA diagnosed according to the criteria of the American College of Rheumatology. DNA and phenotypic data from a healthy control population was obtained from Genome Database of Latvian Population. Genotypes were obtained by direct sequencing. Single-nucleotide polymorphisms (SNPs) were studied and frequencies of alleles and genotypes were compared between patients and controls. A P value less than 0.05 was accepted as statistically significant. There were no significant differences in the distribution of alleles and genotypes between RA patients and the control group. The frequencies of IL-18-607C/A and -656G/T genotypes differed between patients and the control group in women (P = 0.084 and 0.097). Heterozygous genotypes -607CA and -656GT occurred more frequently in the RA group than in the control (P = 0.046, P = 0.060), and this difference was also significant for the only women groups (P = 0.041,P = 0.054). The heterozygous states -607CA and -656GT of IL-18 gene affect susceptibility to RA. On the basis of investigated IL-18 polymorphisms, female patients with RA seem to represent a separate disease subgroup.

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Novel Norrie disease gene mutations in Chinese patients with familial exudative vitreoretinopathy

BMC Ophthalmology ◽

10.1186/s12886-021-01852-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Li-Yun Jia ◽

Kai Ma

Keyword(s):

Disease Gene ◽

Direct Sequencing ◽

Venous Blood ◽

Gene Mutations ◽

Chinese Patients ◽

Control Group ◽

Coding Region ◽

Exon 2 ◽

Norrie Disease ◽

Familial Exudative Vitreoretinopathy

Abstract Purpose This study aims to analyze the Norrie disease gene (NDP) variants in patients with familial exudative vitreoretinopathy (FEVR) and their clinical features. Methods Thirty-three Chinese patients (22 familial and 11 simplex) who were diagnosed as FEVR underwent detailed ocular examinations in Beijing Tongren Hospital. Peripheral venous blood was drawn from the patients and their family members for the extraction of genomic DNA. All exons of NDP gene were analyzed by direct sequencing of PCR-amplified DNA fragments. Results Four novel mutations in NDP gene were identified in four X-linked FEVR families: a C → T transversion, c. 625C → T, in exon 3, resulting in a serine-to-proline change in codon 73 (S73P); a C → G transition, c. 751C → G, in exon 3, resulting in an arginine-to-glycine change in codon 115 (R115G); a T → C transversion of nucleotide 331 at 5’UTR in exon 2 (c.331 T → C); and a C → T transversion of the nucleotide 5 in intron 1 (IVS1 + 5C → T). The mutations were not present in the control group (n = 100). Conclusions Our results extend the spectrum of NDP gene mutations. The mutations in the non-coding region of NDP may play a crucial role in the pathogenesis of FEVR.

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β2-Adrenoreceptor Polymorphisms in Asthmatic Patients

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-8.1.22 ◽

2003 ◽

Vol 8 (1) ◽

pp. 22-28 ◽

Cited By ~ 1

Author(s):

Saeed Binaei ◽

Sahar M. Rashed ◽

Michael L. Christensen

Keyword(s):

Smooth Muscles ◽

Upstream Region ◽

Significant Implication ◽

Nucleotide Polymorphisms ◽

Coding Region ◽

Nocturnal Asthma ◽

Asthmatic Patients ◽

Asthma Patients ◽

Bronchial Dilatation ◽

Β2 Agonists

β2-adrenergic receptors (β2AR) are GTP-binding protein (G-protein) coupled receptors widely distributed in human tissue. Inhaled β2-agonist drugs exert their primary effect on the β2AR of bronchial smooth muscles, causing relaxation and bronchial dilatation. Polymorphisms in the β2AR gene have been identified, which may affect responsiveness to β2-agonists and disease severity in asthmatics. Nine single nucleotide polymorphisms (SNPs) within the coding region and eight SNPs within in the 5′ upstream region of the β2AR gene have been identified. The two most studied polymorphisms are mutations in the coding region at codon 16, Arg to Gly (Arg16Gly) and at codon 27, Gln to Glu (Gln27Glu). Evidence suggests that carriers of Gly16, as well as carriers of Gln27, are prone to down-regulation of β2AR. Patients who are homozygous for Arg16 and/or Glu 27 may be more susceptible to tachyplaxis with chronic use of β2-agonists. Although β2AR polymorphism is not related to the severity of asthma, patients with nocturnal asthma have higher frequency of Gly16. A polymorphism in the 5′ upstream region, 5′ leader cistron (5′LC), encodes for a protein that regulates mRNA transcription. The Cys19 polymorphism in the 5′LC is associated with higher expression of β2AR. More recent studies have focused on combinations of polymorphisms across the gene region (haplotypes). The interaction of multiple SNPs within a haplotype may control β2AR function resulting in different phenotypic response in patients with asthma. β2AR polymorphism may have a significant implication in the pathophysiology of asthma and therapeutic response.

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Genetic characterization and identification of single nucleotide polymorphisms of ATP1A1 gene in Indian humped cattle

Indian Journal of Animal Research ◽

10.18805/ijar.7082 ◽

2015 ◽

Author(s):

A. Barani ◽

K. P. Ramesha ◽

M. Basavaraju ◽

Akhila Rao ◽

TVL. Narasimha Rao

Keyword(s):

Heat Stress ◽

Heat Tolerance ◽

Direct Sequencing ◽

Bos Indicus ◽

Plasma Potassium ◽

Single Strand Conformation Polymorphism ◽

Integral Membrane Protein ◽

Nucleotide Polymorphisms ◽

Coding Region ◽

Information Index

Climate change in India is likely to aggravate the heat stress in dairy animals due to rise in temperature coupled with increased precipitation. In animals heat stress affects the alteration of plasma Potassium (K (+)) and Sodium Na (+) ions. ATP1A1 gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+ -ATPases. Na+/K+ -ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na+ and K+ ions across the plasma membrane. The present study is aimed to investigate the polymorphisms in the entire coding region of ATP1A1 gene in Bos indicus (Deoni) cattle by PCR- Single-Strand Conformation Polymorphism (PCR- SSCP) and direct sequencing of variants. Sequence analysis showed 16 SNPs, of which 5 SNPs were in the coding region and the remaining 11 SNPs were detected in the non-coding region of ATP1A1 gene. All the observed variations in the coding regions of ATP1A1 gene were silent mutations. The genotypic, allelic frequencies, c<sup>2</sup> test for Hardy-Weinberg equilibrium and Shannon’s information index were calculated using POPGENE-32. The study revealed a high degree of genetic variability in ATP1A1 gene in the Deoni cattle population which indicated the utility of this gene for further studies for identification of markers associated with heat tolerance in Indian humped cattle for using in marker assisted selection for heat tolerance.

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Mutational Screening of FGFR1, CER1, and CDON in a Large Cohort of Trigonocephalic Patients

The Cleft Palate-Craniofacial Journal ◽

10.1597/04-206.1 ◽

2006 ◽

Vol 43 (2) ◽

pp. 148-151 ◽

Cited By ~ 13

Author(s):

Fernanda Sarquis Jehee ◽

Luis G. Alonso ◽

Denise P. Cavalcanti ◽

Chong Kim ◽

Steven A. Wall ◽

...

Keyword(s):

High Performance ◽

Direct Sequencing ◽

Nucleotide Polymorphisms ◽

Related Gene ◽

Inclusion Criteria ◽

Coding Region ◽

Single Nucleotide ◽

Metopic Synostosis ◽

Mutational Screening ◽

Johns Hopkins University

Objective Screen the known craniosynostotic related gene, FGFR1 (exon 7), and two new identified potential candidates, CER1 and CDON, in patients with syndromic and nonsyndromic metopic craniosynostosis to determine if they might be causative genes. Design Using single-strand conformational polymorphisms (SSCPs), denaturing high-performance liquid chromatography, and/or direct sequencing, we analyzed a total of 81 patients for FGFR1 (exon 7), 70 for CER1, and 44 for CDON. Patients Patients were ascertained in the Centro de Estudos do Genoma Humano in São Paulo, Brazil (n = 39), the Craniofacial Unit, Oxford, U.K. (n = 23), and the Johns Hopkins University, Baltimore, Maryland (n = 31). Clinical inclusion criteria included a triangular head and/or forehead, with or without a metopic ridge, and a radiographic documentation of metopic synostosis. Both syndromic and nonsyndromic patients were studied. Results No sequence alterations were found for FGFR1 (exon 7). Different patterns of SSCP migration for CER1 compatible with the segregation of single nucleotide polymorphisms reported in the region were identified. Seventeen sequence alterations were detected in the coding region of CDON, seven of which are new, but segregation analysis in parents and homology studies did not indicate a pathological role. Conclusions: FGFR1 (exon 7), CER1, and CDON are not related to trigonocephaly in our sample and should not be considered as causative genes for metopic synostosis. Screening of FGFR1 (exon 7) for diagnostic purposes should not be performed in trigonocephalic patients.

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Association between MicroRNA-4669 Polymorphism and Ischemic Stroke in a Korean Population

Disease Markers ◽

10.1155/2019/7238319 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9

Author(s):

Seoung-Jin Hong ◽

Su Kang Kim ◽

Dong Hwan Yun ◽

Jinmann Chon ◽

Hae Jeong Park

Keyword(s):

Ischemic Stroke ◽

Pilot Study ◽

Direct Sequencing ◽

Strong Association ◽

Additive Model ◽

Korean Population ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Control Subjects ◽

Weak Association

Recent studies have explored the association between single-nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) and ischemic stroke (IS). In particular, the associations of rs2910164 (miRNA-146A), rs11614913 (miRNA-196A2), and rs3746444 (miRNA-499A) were intensively studied in IS. In this study, we investigated the associations between SNPs in miRNAs and IS including rs2910164, rs11614913, and rs3746444 in a Korean population. For a pilot study, we selected 19 SNPs in pre-miRNA region (including mature miRNA region) and genotyped in 140 IS patients and 240 control subjects using the Fluidigm Dynamic Array. Our pilot study showed a weak association of rs79402775 in miRNA-933 (p=0.044) and a relatively strong association of rs35196866 in miRNA-4669 (p=0.016) with IS. From the pilot study, we selected rs79402775, rs35196866, and rs7202008 (miRNA-2117; p=0.055) as candidate miRNA SNPs on IS and further genotyped these SNPs in 264 IS patients and 455 control subjects using direct sequencing. In addition, we further analyzed the associations of rs2910164, rs11614913, and rs3746444 that have been intensively studied in previous studies. In the further analysis, we found the significant association between rs35196866 and IS (p=0.0014 in additive model and p=0.00015 in dominant model; p=0.00037 in allele frequency analysis). However, the association between rs2910164, rs11614913, rs3746444, rs79402775, and rs7202008 and IS was not shown. These results suggest that miRNA-4669 may be involved in the susceptibility of IS.

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The association between the presence of fat mass and obesity-associated gene (FTO) and the incidence of obesity in Iraqi persons in Holy Kerbala

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v10i4.1747 ◽

2019 ◽

Vol 10 (4) ◽

pp. 3644-3648

Author(s):

Zainab Nizar Jawad ◽

Kamal Abul Rasool

Keyword(s):

Fat Mass ◽

Strong Association ◽

Obese Group ◽

Control Group ◽

Specific Gene ◽

Nucleotide Polymorphisms ◽

Predisposing Factor ◽

Single Nucleotide ◽

Underlying Causes ◽

Fto Rs9939609

Obesity is regarded nowadays as one of the worldwide medical and psychosocial problem so that many researches had been dealt with the underlying causes of resistant obesity and increased body mass index “BMI”. Recent data demonstrate the strong association between the presence of obesity with specific gene called fat mass and obesity associated gene (FTO). Many single nucleotide polymorphisms (SNPs) was detected that are discovered that closely related to the increased incidence of obesity among populations, notably rs9939609 and rs17817449 SNPs. To evaluate the presence of these SNPs as a predisposing factor in obese persons with BMI exceeds 30. A 100 obese persons were selected randomly along with 50 body-fitted people as a control group. Molecular detection of these SNPs was done by RT-PCR followed by statistical analysis. there was significant increase in expression of AA genotype of FTO rs9939609 SNP in obese persons in comparison to non-obese group (0.60 ± 0.04 versus 0.28 ± 0.06 respectively at P> 0.002) and significant increase in expression of GG genotype of FTO rs1781744 SNP in obese persons in comparison to non-obese group 0.59 ± 0.04 versus 0.22 ± 0.05 respectively at P> 0.001)

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