Search Results (25)

Background: Depression is one of the most prevalent mental health disorders worldwide, affecting a significant proportion of the global population. Its etiology is complex and influenced by the interaction of environmental factors and genetic variations. In Mexico, it has been reported that 41.3% of the population exhibits depressive symptoms. Previous studies have suggested that susceptibility to depression may be associated with the C-1019G (rs6295) polymorphism in the serotonin 1A (5-HT1A) receptor gene. Objective: In this study, we aimed to evaluate the association between the C-1019G polymorphism and depressive symptoms in a rural Mexican population. Methods: Using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP), we examined the effect of C-1019G on depression symptoms, as evaluated by the Beck Depression Inventory. Data were obtained from 83 volunteers; individuals with depressive symptoms and those with a healthy mood were compared. Results: The results showed that the homozygous C/C genotype was found significantly more frequently in the control group than in individuals with depressive symptoms, particularly among men, and is thus associated with a decreased risk of depressive symptomatology. Conclusions: The C/C genotype could protect against susceptibility to developing depressive symptoms in a rural population in Mexico. Full article

Background/Objectives: Hashimoto’s thyroiditis (HT) is the most common cause of hypothyroidism during childhood and adolescence. Children and adolescents with HT have an increased susceptibility to the development of thyroid nodules and thyroid cancer. Among the genetic causes of thyroid cancer, the 677C>T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene is also reported. This study investigated for the first time the association between the 677C>T polymorphism (rs1801133) of the MTHFR gene and HT in children and adolescents. Methods: This case–control study included 130 children and adolescents with HT and 130 healthy controls. The 677C>T polymorphism of the MTHFR gene was studied in all participants with Restriction Fragment Length Polymorphism (RFLP) methodology for genetic variance analysis. Results: Children and adolescents with HT presented approximately 2.5 times more frequently the T allele sequences (CT and TT variants) and the T alleles in total for the 677C>T polymorphism of the MTHFR gene compared to the healthy population (OR: 2.56, CI: 1.53–4.21 and OR: 2.57, CI: 1.59–4.16, respectively). Children and adolescents with HT and T allele sequences (CT and TT variants) exhibited abnormal thyroglobulin antibodies (anti-TG) two times more frequently compared to those with the wild-type (CC) sequence in the same population (OR: 2.13, CI: 1.04–4.389). Conclusions: Children and adolescents with HT showed an increased frequency of T allele sequences (CT and TT variants) and total T alleles of the 677C>T polymorphism of the MTHFR gene compared to the healthy population. Full article

Tryptophan hydroxylase 2 (TPH2) hydroxylates L-tryptophan to L-5-hydroxy tryptophan—the key step of 5-HT synthesis in the mammalian brain. Some mutations in the human hTPH2 gene are associated with psychopathologies and resistance to antidepressant therapy. The C1473G polymorphism in the mouse Tph2 gene decreases the TPH2 activity in the mouse brain. In the present paper, B6-1473C and B6-1473G congenic mice that were different only in the C > G substitution were used. The molecular mechanism of decrease in the mutant enzyme activity and some physiological and behavioral traits affected by this mutation were revealed for the first time. Analysis of thermal denaturation curves in vitro revealed that the C > G substitution reduces the free energy of denaturation, stability and lifetime of mutant TPH2. Later, we evaluated the effect of the 1473G allele on the hierarchical state, competition for a sexual partner in adult mice, mouse embryos, hind legs dystonia and the response to LPS treatment in young mice. No effect of this mutation on the hierarchical state and competition for a female was observed in adult males. The C > G substitution does not affect survival, body mass or the TPH activity in the brain of 19-day-old mouse embryos. At the same time, we found that the 1473G allele causes hind legs dystonia in juvenile (3 weeks old) mice, which can affect their escape capability in threatening situations. Moreover, a significant increase in the vulnerability to LPS in juvenile B6-1473G males was shown: a single ip LPS administration killed about 40% of young mutant mice, but not wild-type ones. The body mass of mutant males was lower compared to wild-type ones, which also can indirectly decrease their concurrent and reproductive success. Full article

Objectives: This study aims to show the distribution of angiotensin-converting enzyme (ACE) rs1799752 (I>D) gene insertion/deletion (I/D) polymorphism and angiotensin II receptor type 1 (AGTR1) rs5186 (A>C) gene polymorphism in adolescents with hypertension (HT) and type 1 diabetes (T1D), as well as its association with hypertension and the diurnal variation of mean blood pressure (dipping phenomenon). Methods: A cross-sectional study was conducted involving 118 adolescents diagnosed with T1D who underwent clinical and laboratory investigations, genetic analyses, and 24 h ambulatory blood pressure monitoring. The genotype frequencies were compared between adolescents with HT and those with normal blood pressure. Additionally, the genotype frequencies were compared between dippers and non-dippers. Results: Patients with HT were more likely to be female and exhibited significantly poorer glycemic control and higher triglycerides, along with increased body mass index and daily insulin dosage. The prevalence of ACE rs1799752 genotypes in the hypertensive group was 20% II, 66.7% ID, and 13.3% DD, which did not significantly differ from the normal blood pressure group with 29.1% II, 53.4% ID, and 17.5% DD (p = 0.625). The prevalence of AGTR1 rs5186 genotypes in the hypertensive group was 53.3% AC, 40% AA, and 6.7% CC, which also did not significantly differ from the normal blood pressure group with 39.8% AC, 52.4% AA, and 7.8% CC (p = 0.608). A total of 46% of the patients exhibited non-dipping phenomena. The prevalence of non-dippers among the ACE genotypes was 13% DD, 33.3% II, and 53.7% ID (p = 0.369), while for the AGTR1 genotypes, it was 50% AA, 42.6% AC, and 7.4% CC (p = 0.976). Conclusions: Our results indicate that in our adolescents with T1D, clinical and metabolic factors such as higher body mass index, triglycerides, suboptimal glycemic control, and female gender are more indicative of the development of hypertension than ACE and AGTR1 gene polymorphisms. A potential reason for this finding could be the young age of the patients or the relatively small size of the study group. Future research involving larger sample sizes is needed to further investigate the genetic predisposition for the development of hypertension. Full article

Lipizzan is a famous horse breed dating back to 1580 when the original stud of Lipica was established by the Hasburg Archduke Charles II. Currently, the Italian State Stud of Lipizzan Horses (ASCAL) is a conservation nucleus managed through strict mating rules where mitochondrial DNA sequences are used to verify the correct assignment of mares to a historical pedigree maternal lineage. Here, we analyzed the D-loop sequences of Lipizzan horses from the ASCAL in Monterotondo (Rome, Italy) in order to confirm their pedigree assignment to known female founder families. The concurrent investigation of the paternal counterpart based on variation in the male-specific region of the Y chromosome (MSY) showed a prevalence of HT02 (80%), typical of the Neapolitan/Oriental wave. The mtDNA polymorphisms identified shaped nine haplotypes that were unequivocally assigned to each of nine classical mare families of the stud (Africa, Almerina, Argentina, Deflorata, Djebrin, Fistula, Ivanka, Sardinia, Spadiglia), while the Europa and Theodorosta families shared a tenth haplotype. New polymorphisms were identified in a not previously studied region (np 16100–16350). The mtDNA phylogenetic analysis revealed that the Lipizzans of the Monterotondo stud belong to six haplogroups (B, C, G, L, M, Q), out of the 18 recorded for the equine species. This work enabled us to identify and preserve ten haplotypes from the historical maternal lines in a small stud kept in genetic segregation for over 100 years. Full article

Metabolic and bariatric surgery (MBS) effectively treats obesity and related comorbidities, though individual responses vary. This systematic review examines how genetic variants influence MBS outcomes in morbidly obese patients. A comprehensive search in PubMed, Embase, Medline, and the Cochrane Library identified 1572 studies, with 52 meeting the inclusion criteria. Two reviewers independently filtered and selected studies, including relevant cross-references. Research focused on polymorphisms in genes such as UCP2, UCP3, 5-HT2C, MC4R, FKBP5, FTO, CAT haplotypes, LYPAL-1, PTEN, FABP-2, CNR1, LEP656, LEP223, GLP-1R, APOA-1, APOE, ADIPOQ, IL-6, PGC1a, TM6SF2, MBOAT7, PNPLA3, TCF7L2, ESR1, GHSR, GHRL, CD40L, DIO2, ACSL5, CG, TAS2R38, CD36, OBPIIa, NPY, BDNF, CLOCK, and CAMKK2. Most studies explored associations with post-surgery weight loss, while some examined metabolic, cardiovascular, taste, and eating behavior effects as well. Understanding the role of genetic factors in weight loss and metabolic outcomes post-MBS can help tailor personalized treatment plans for improved efficacy and long-term success. Further research with larger sample sizes and extended follow-up is needed to clarify the effects of many genetic variants on MBS outcomes in morbidly obese patients. Full article

Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) are common autoimmune endocrine disorders in children. Studies indicate that apart from environmental factors, genetic background significantly contributes to the development of these diseases. This study aimed to assess the prevalence of selected single-nucleotide polymorphisms (SNPs) of Il7R, CD226, CAPSL, and CLEC16A genes in children with autoimmune thyroid diseases. We analyzed SNPs at the locus rs3194051, rs6897932 of IL7R, rs763361 of CD226, rs1010601 of CAPSL, and rs725613 of CLEC16A gene in 56 HT patients, 124 GD patients, and 156 healthy children. We observed significant differences in alleles IL7R (rs6897932) between HT males and the control group (C > T, p = 0.028) and between all GD patients and healthy children (C > T, p = 0.035) as well as GD females and controls (C > T, p = 0.018). Moreover, the C/T genotype was less frequent in GD patients at rs6897932 locus and in HT males at rs1010601 locus. The presence of the T allele in the IL7R (rs6897932) locus appears to have a protective effect against HT in males and GD in all children. Similarly, the presence of the T allele in the CAPSL locus (rs1010601) seems to reduce the risk of HT development in all patients. Full article

Rice (Oryza sativa L.) is an important cereal crop worldwide due to its long domestication history. North-Eastern India (NEI) is one of the origins of indica rice and contains various native landraces that can withstand climatic changes. The present study compared NEI rice landraces to a check variety for phenological, morpho-physiological, and yield-associated traits under high temperatures (HTs) and elevated CO₂ (eCO₂) levels using molecular markers. The first experiment tested 75 rice landraces for HT tolerance. Seven better-performing landraces and the check variety (N22) were evaluated for the above traits in bioreactors for two years (2019 and 2020) under control (T1) and two stress treatments [mild stress or T2 (eCO₂ 550 ppm + 4 °C more than ambient temperature) and severe stress or T3 (eCO₂ 750 ppm + 6 °C more than ambient temperature)]. The findings showed that moderate stress (T2) improved plant height (PH), leaf number (LN), leaf area (LA), spikelets panicle⁻¹ (S/P), thousand-grain weight (TGW), harvest index (HI), and grain production. HT and eCO₂ in T3 significantly decreased all genotypes’ metrics, including grain yield (GY). Pollen traits are strongly and positively associated with spikelet fertility at maturity and GY under stress conditions. Shoot biomass positively affected yield-associated traits including S/P, TGW, HI, and GY. This study recorded an average reduction of 8.09% GY across two seasons in response to the conditions simulated in T3. Overall, two landraces—Kohima special and Lisem—were found to be more responsive compared to other the landraces as well as N22 under stress conditions, with a higher yield and biomass increment. SCoT-marker-assisted genotyping amplified 77 alleles, 55 of which were polymorphic, with polymorphism information content (PIC) values from 0.22 to 0.67. The study reveals genetic variation among the rice lines and supports Kohima Special and Lisem’s close relationship. These two better-performing rice landraces are useful pre-breeding resources for future rice-breeding programs to increase stress tolerance, especially to HT and high eCO₂ levels under changing climatic situations. Full article

In this study, galeite, Na₁₅(SO₄)₅ClF₄ and schairerite, Na₂₁(SO₄)₇ClF₆ were investigated via in situ single-crystal X-ray diffraction in the temperature range of 300–750 K. Galeite and schairerite are trigonal, P31m, a = 12.1903(2), c = 13.9454(2) Å, V = 1794.69(6) ų, and Z = 3 (R₁ = 0.0273, 300 K) for galeite and a = 12.1859(3), c = 19.3080(6) Å, V = 2483.04(14) ų, and Z = 3 (R₁ = 0.0334, 300 K) for schairerite. The crystal structures of galeite and schairerite are based upon frameworks consisting of alternating face- and corner-sharing fluorine- and chlorine-centered octahedra. Galeite and schairerite can be attributed to 5H (galeite) and 7H (schairerite) antiperovskite polytypes, respectively. It was observed that schairerite undergoes at least one reversible phase transition before it starts to lose its crystallinity at 750 K. This phase transition occurs in the temperature range of 550–600 K. The high-temperature modification of schairerite is trigonal, with the centrosymmetric space group P-3m1 and the unit-cell parameters a = 7.0714(2), c = 19.5972(7) Å, V = 848.66(6) ų, and Z = 1. Galeite is stable up to 600 K. The crystal structures of minerals expand anisotropically, and, in both cases, the strongest thermal expansion was parallel to the modules of face-sharing anion-centered octahedra. The structural complexity analysis showed that galeite is complex (695.175 bits/cell) and that the LT-modification of schairerite is very complex (1064.990 bits/cell), whereas its HT-modification is intermediate in complexity (256.755 bits/cell). The complexities of LT- and HT-polymorphs of schairerite are consistent with the general observations regarding structures with positional disorder: complexity decreases with increasing temperature, and simpler polymorphs have lower physical density. Full article

Hashimoto’s thyroiditis (HT) is a chronic autoimmune disorder characterized by the production of autoantibodies against the thyroid gland. Different studies have shown that several genes may be associated with HT, which explains why patients often have family members with thyroiditis or other autoimmune diseases. The aim of this case-control study was to evaluate the correlation between polymorphisms at the level of exon 1 from the CTLA-4 gene and the susceptibility to developing HT. In this study, we found that there is no statistically significant association between the polymorphism rs231775 (A22G in exon 1) of the CTLA-4 gene and a genetic predisposition to HT. In contrast, a strong association was discovered for the first time between C55A in exon 1 of the CTLA-4 gene and HT. Our findings suggest that there is a genetic relationship between the CTLA-4 (+55A/C) genotype and the seropositivity against thyroid autoantigens, such as anti-thyroid peroxidase (ATPO) and anti-thyroglobulin antibodies (ATG). Full article

Commiphora gileadensis (L.) C. Chr is a perennial plant existing mainly in the southern and western mountains of the Arabian Peninsula. In the Makkah province, the remaining populations are threatened by many factors such as overcutting, overgrazing, and urban developments. These dangers are expected to be aggravated by the progression of aridification factors arising from climate change. To overcome the decline in remaining populations of this valuable species, a timely evaluation of the population’s genetic variables and genetic structure is vital for the conservation of existing C. gileadensis populations. In this study, we used 61 SSR primers to achieve this objective. Only 50 loci showed polymorphisms, which led to further analysis of the population genetics for 600 genotypes that were collected from 50 populations of C. gileadensis found in 10 different sites in the Makkah region: Gebel Al Muliesaa, Wadi Albathna, Wadi Houra, Wadi Albaidaa, Wadi Elebiedia, Gebel Kniethl, Wadi Sayaa, Wadi Elbarasa, Wadi Alfawara, and Wadi Alkharar. The results showed an obvious decrease in genetic diversity variables in all studied populations. The range of PPL was between 8 and 40; additionally, the low H_T value of 0.804 and the high value of inbreeding, F_is = 0.238, reflected a severe lack of heterozygotes. High levels of F_ST and G_ST and low gene flow indicate considerable segregation among the C. gileadensis populations, which creates a barrier to gene migration. Our data suggest the need for conservation planning for C. gileadensis in order to avoid the species’ forthcoming extinction. Efforts should be largely oriented around managing water consumption, prohibiting overcutting and overgrazing, and establishing appropriate seed banks. Full article

The complex role of the serotonin system in respiratory function and inflammatory diseases such as asthma is unclear. Our study investigated platelet serotonin (5-HT) levels and platelet monoamine oxidase B (MAO-B) activity, as well as associations with HTR2A (rs6314; rs6313), HTR2C (rs3813929; rs518147), and MAOB (rs1799836; rs6651806) gene polymorphisms in 120 healthy individuals and 120 asthma patients of different severity and phenotypes. Platelet 5-HT concentration was significantly lower, while platelet MAO-B activity was considerably higher in asthma patients; however, they did not differ between patients with different asthma severity or phenotypes. Only the healthy subjects, but not the asthma patients, carrying the MAOB rs1799836 TT genotype had significantly lower platelet MAO-B activity than the C allele carriers. No significant differences in the frequency of the genotypes, alleles, or haplotypes for any of the investigated HTR2A, HTR2C and MAOB gene polymorphisms have been observed between asthma patients and healthy subjects or between patients with various asthma phenotypes. However, the carriers of the HTR2C rs518147 CC genotype or C allele were significantly less frequent in severe asthma patients than in the G allele carriers. Further studies are necessary to elucidate the involvement of the serotonergic system in asthma pathophysiology. Full article

Background: Seeing that there are no data about associations between serotonin gene polymorphism and tryptophan catabolite concentration during PEG-IFN-α2a treatment, the aim of the current study is to examine (a) the associations between polymorphisms within the HTR1A, TPH2, and 5-HTT genes and the severity of depression symptoms and (b) the relationships among rs6295, rs4570625, and 5-HTTLPR rs25531polymorphisms and indoleamine 2,3-dioxygenase (IDO) activity, as well as kynurenine (KYN), tryptophan (TRP), kynurenic acid (KA), and anthranilic acid (AA) concentrations. Materials and methods: The study followed a prospective, longitudinal, single-center cohort design. The severity of the depressive symptoms of 101 adult patients with chronic HCV infections was measured during PEG-IFN-α2a/RBV treatment. We used the Montgomery–Åsberg Depression Rating Scale (MADRS) to assess the severity of depressive symptoms. The subjects were evaluated six times—at baseline and at weeks 2, 4, 8, 12, and 24. At all the time points, MADRS score, as well as KYN, TRP, KA, and AA concentrations, and IDO activity were measured. At baseline, rs6295, rs4570625, and 5-HTTLPR rs25531polymorphisms were assessed. Results: Subjects with C/C genotypes of 5-HT1A and lower-expressing alleles (S/S, L_G/L_G, and S/L_G) of 5-HTTLPR scored the highest total MADRS scores and recorded the highest increase in MADRS scores during treatment. We found associations between TRP concentrations and the TPH-2 and 5-HTTLPR rs25531 genotypes. Conclusions: Our findings provide new data that we believe can help better understand infection-induced depression as a distinct type of depression. Full article

Major depressive disorder (MDD) is the leading cause of disability worldwide. Treatment with antidepressant drugs (ATD), which target monoamine neurotransmitters including serotonin (5HT), are only modestly effective. Monoamine oxidase (MAO) metabolizes 5HT to 5-hydroxy indoleacetic acid (5HIAA). Genetic variants in the X-chromosome-linked MAO-encoding genes, MAOA and MAOB, have been associated with clinical improvement following ATD treatment in depressed patients. Our aim was to analyze the association of MAOA and MAOB genetic variants with (1) clinical improvement and (2) the plasma 5HIAA/5HT ratio in 6-month ATD-treated depressed individuals. Clinical (n = 378) and metabolite (n = 148) data were obtained at baseline and up to 6 months after beginning ATD treatment (M6) in patients of METADAP. Mixed-effects models were used to assess the association of variants with the Hamilton Depression Rating Scale (HDRS) score, response and remission rates, and the plasma 5HIAA/5HT ratio. Variant × sex interactions and dominance terms were included to control for X-chromosome-linked factors. The MAOA rs979605 and MAOB rs1799836 polymorphisms were analyzed. The sex × rs979605 interaction was significantly associated with the HDRS score (p = 0.012). At M6, A allele-carrying males had a lower HDRS score (n = 24, 10.9 ± 1.61) compared to AA homozygous females (n = 14, 18.1 ± 1.87; p = 0.0067). The rs1799836 polymorphism was significantly associated with the plasma 5HIAA/5HT ratio (p = 0.018). Overall, CC/C females/males had a lower ratio (n = 44, 2.18 ± 0.28) compared to TT/T females/males (n = 60, 2.79 ± 0.27; p = 0.047). The MAOA rs979605 polymorphism, associated with the HDRS score in a sex-dependent manner, could be a useful biomarker for the response to ATD treatment. Full article

A decrease in serotonergic transmission throughout the brain is among the earliest pathological changes in Alzheimer’s disease (AD). Serotonergic receptors are also affected in AD. Polymorphisms in genes of serotonin (5HT) receptors have been mostly associated with behavioral and psychological symptoms of dementia (BPSD). In this study, we examined if AD patients carrying different genotypes in 5HTR1B rs13212041, 5HTR2A rs6313 (T102C), 5HTR2C rs3813929 (−759C/T), and 5HTR6 rs1805054 (C267T) polymorphisms have a higher risk of faster disease progression (assessed by neuropsychological testing), are more prone to develop AD-related pathology (reflected by levels of cerebrospinal fluid [CSF] AD biomarkers), or have an association with an apolipoprotein E (APOE) haplotype. This study included 115 patients with AD, 53 patients with mild cognitive impairment (MCI), and 2701 healthy controls. AD biomarkers were determined in the CSF of AD and MCI patients using enzyme-linked immunosorbent assays (ELISA), while polymorphisms were determined using either TaqMan SNP Genotyping Assays or Illumina genotyping platforms. We detected a significant decrease in the CSF amyloid β_1–42 (Aβ_1–42) and an increase in p-tau₁₈₁/Aβ_1–42 ratio in carriers of the T allele in the 5HTR2C rs3813929 (−759C/T) polymorphism. A significantly higher number of APOE ε4 allele carriers was observed among individuals carrying a TT genotype within the 5HTR2A T102C polymorphism, a C allele within the 5HTR1B rs13212041 polymorphism, and a T allele within the 5HTR6 rs1805054 (C267T) polymorphism. Additionally, individuals carrying the C allele within the 5HTR1B rs13212041 polymorphism were significantly more represented among AD patients and had poorer performances on the Rey–Osterrieth test. Carriers of the T allele within the 5HTR6 rs1805054 had poorer performances on the MMSE and ADAS–Cog. As all four analyzed polymorphisms of serotonin receptor genes showed an association with either genetic, CSF, or neuropsychological biomarkers of AD, they deserve further investigation as potential early genetic biomarkers of AD. Full article