Irritable bowel syndrome (IBS) is a gut‐brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation‐predominant IBS (IBS‐C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta‐analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS‐C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow‐up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS‐C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.
PPARGC1A is involved in many metabolic processes including normal mitochondrial biogenesis, oxidation of glucose and lipids and transport of glucose into skeletal muscles. Previous researches linked this polymorphism with the higher risk of developing type 2 diabetes, metabolic syndrome and obesity. The aim of the study was to investigate the association of Gly482Ser with body mass index (BMI), fasting glucose levels and lipid profile in Serbian adolescents. The study included 147 boys and 150 girls, 15 years of age. Anthropometric and biochemical parameters were recorded. Cardiovascular and malignant diseases, type 2 diabetes, cerebral palsy and genetics syndrome were criteria for exclusion. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (RFLP) assay. The results showed that boys carriers of GG genotype had statistically higher mean values of TC compared to the boys who were carriers of GA+AA genotypes (p=0.033). However, statistical significance was not obtained for the other analyzed parameters. Furthermore, in the group of overweight and obese children, higher mean values of TC and LDL-C were observed in the carriers of GG genotype compared to carriers of GA+AA genotype for all the adolescents, as well as in the group of girls. No correlation was observed for values of BMI, fasting blood glucose and levels of triglycerides. To confirm these results, further research with larger sample size and non-genetics factor taking into consideration, would be of great interest.
Background/Aim: Irritable bowel syndrome (IBS) belongs to the gastrointestinal disorders characterised by abdominal discomfort and pain, altered constipation, diarrhoea and stomach distension. The aim was to assess relationship between the selected genetic polymorphisms with IBS, their combined genotype effect as well as to assess a difference in the distribution of allele and genotype frequencies of selected loci between case and control group. Methods: This was a prospective study which included 29 participants, 20 individuals diagnosed with IBS based on Rome III criteria and 9 healthy individuals. The study analysed the selected genetic polymorphisms as possible risk factors for IBS according to the model of the case-control study. Genotyping was performed for FKBP5, DRD2 and DAT polymorphisms qualified as risk factors for IBS in previous researches. Results: The results revealed a significant association between DAT polymorphism with IBS, both, at the allelic level (p = 0.006) and genotype level (p = 0.031). Individuals with 434 allelic variant in the genotype have six time higher probability for developing IBS, in comparison to the individuals without this allelic variant. The statistical association between other analysed polymorphism and IBS was not reached. The analysis of combined effects of selected polymorphisms revealed no association with IBS, except FKBP5 and DAT which result was at the level of statistical significance (p = 0.05). Conclusion: Further analysis which would include DAT polymorphism with larger sample size, as well as other genes involved in dopamine neurotransmitter system would be of great interest to define closer conclusion of IBS aetiology.
Initial testing of children with psychomotor delays considers karyotype analysis and metabolic tests. However, introduction of Array Comparative Genomic Hybridization (ACGH) has become the standard method of diagnostics worldwide. ACGH is a highly sensitive method which enables detection of unbalanced chromosomal aberrations and aneuploidies. In this case report, a patient is a sixteen year old girl born to unrelated parents with mild mental retardation and psychomotor delay, hyperacusis, epilepsy, silent nasal speech, clinodactyly of the V finger on left hand, as well as low set ears. Patient had a karyotype interpreted as normal using GTG band analysis. Array CGH was performed using Agilent SurePrint G3 custom CGH+SNP Microarray 8x60K (UCSC, hg19, NCBI Build 37, February,2009). Results were analyzed by CytoGenomics 3.0 Agilent software. Results of aCGH revealed clinically significant duplication of 17q25.1-q25.3 region with the size of~7.96Mb. Within the duplicated region 217 genes are present, of which 36 are described as OMIM morbid. Duplications of similar size are described in DECIPHER date base in patients with psychomotor delay, hyperactivity and neoplasm of CNS. Besides duplication, a ~755kb clinically significant deletion was detected in the 17q25.3 region. Deletion involves 18 genes of which 2 are described as OMIM morbid: TBCD (MIM604649) and ZNF750 (MIM610226). Patient with similar deletion was described in DECIPHER date base with notable psychomotor delay. Based on these results FISH analysis is recommended for both parents in order to determine the possible carrier of inversion in the region of 17qter.
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