Receptor Gene Single Nucleotide Polymorphisms Research Articles

Relation of T Cell Profile with Vitamin D Receptor and Vitamin D-Binding Protein Gene Polymorphisms in Atopy.

Atopic diseases, including atopic dermatitis (AD) and allergic asthma (AA), are characterized by complex immune responses involving various T cells subsets and their cytokine profiles. It is assumed that single nucleotide polymorphisms (SNPs) in the Vitamin D receptor (VDR) gene and the Vitamin D-binding protein (GC) gene are related to the action of Vitamin D and, consequently, play a role in regulating the immune response. However, there is not enough data to unequivocally support the hypothesis about the relationship between T cells profile and VDR or GC SNPs. Two hundred sixty-six subjects (aged > 18 years) were involved in the study: 100 patients with mild or moderate AD, 85 patients with mild or moderate AA, and 81 healthy individuals. Blood cell counts were determined by standard methods. Flow cytometric analysis was used to evaluate CD4+ T-helper (Th) cell subtypes: Th2, Th1, Th17, and T regulatory (Treg) cells in peripheral blood. Measurements of cytokines, total immunoglobulin E (IgE), and Vitamin D levels in serum were evaluated by ELISA. Significantly higher levels of Th1, Th2, and Th17 cells, along with lower levels of Tregs, were found in patients with atopic diseases compared to healthy individuals. Additionally, higher serum levels of interleukin (IL) 5, IL-17A, and transforming growth factor-β1 (TGF-β1), as well as lower levels of IL-10, were observed in patients with atopic diseases than in control. The study established associations between VDR SNPs and immune profiles: the AA genotype of rs731236 was associated with increased Th2 and Th17 cells and a higher Th1/Th2 ratio; the GG genotype of rs731236 was linked to decreased serum IL-10 and TGF-β1 levels; and the TT genotype of rs11168293 was associated with increased IL-10 levels. Additionally, the GG genotype of GC gene SNP rs4588 was associated with reduced Th2 and Th17 lymphocytes, while the TT genotype of rs4588 was linked to decreased IL-10 levels. Furthermore, the CC genotype of rs7041 was associated with higher levels of Th2, Th17, IL-10, and IL-35, as well as reduced levels of TGF-β1, while the GG genotype of rs3733359 was associated with reduced IL-10 levels. In conclusion, our study demonstrates that the Vitamin D receptor gene single nucleotide polymorphisms rs731236 and rs11168293, along with polymorphisms in the Vitamin D-binding protein gene (rs4588, rs7041, rs3733359), are significantly associated with variations in T cell profiles in atopy. These variations may play a crucial role in promoting inflammation and provide insight into the genetic factors contributing to the pathogenesis of atopy.

Effect of weekly vitamin D supplementation on the severity of atopic dermatitis and type 2 immunity biomarkers in children: A randomized controlled trial.

Vitamin D (VD) deficiency is common among patients with atopic dermatitis (AD) and often associated with severity. However, randomized trials of VD supplementation in AD have had equivocal results, and there is little information regarding the effect of VD supplementation on type 2 immunity in AD patients. To investigate the efficacy of VD supplementation to decrease severity of AD and to alter type 2 immunity biomarkers. We performed a randomized, double-blind, placebo-controlled trial. We randomly assigned 101 children with AD to weekly oral vitamin D3 (VD3) or placebo for 6 weeks. The primary outcome was the change in the Severity Scoring of AD (SCORAD). Mean age of subjects was 6.3 ± 4.0 years, and baseline SCORAD was 32 ± 29. At baseline, 57% of children were VD deficient, with no difference between groups. Change in 25(OH)D was significantly greater with VD3 than placebo (+43.4 ± 34.5 nmol/L vs. +2.3 ± 21.2 nmol/L, p < 0.001). SCORAD change at 6 weeks was not different between VD and placebo (-5.3 ± 11.6 vs. -5.5 ± 9.9, p = 0.91). There were no significant between-group differences in change of eosinophil counts, total IgE, Staphylococcal enterotoxin specific IgE, CCL17, CCL22, CCL27, LL-37 or Staphylococcus aureus lesional skin colonization. Vitamin D receptor (VDR) gene single nucleotide polymorphisms FokI, ApaI and TaqI did not modify subjects' response to VD supplementation. Among children with AD, weekly VD supplementation improved VD status but did not modify AD severity or type 2 immunity biomarkers compared to placebo (ClinicalTrials.gov NCT01996423).

Research Note: Association of insulin-like growth factor 1 receptor gene polymorphism with production performance in Savimalt and French Giant meat-type quails

This study aimed to investigate the association of insulin-like growth factor 1 receptor (IGF-1R) gene single nucleotide polymorphisms (SNPs) with growth traits and carcass traits of quail by PCR amplification and direct sequencing technology. Genomic DNA was extracted from blood samples collected from 49 female French Giant (FG) quails and 36 female Savimalt (SV) quails as part of this study. Growth traits and carcass traits were measured and assessed for IGF-1R gene analysis in the 2 meat-type quail strains. The results showed that 2 SNPs (A57G and A72T) of the IGF-1R gene were detected in the 2 quail strains. The A57G (P=0.002) and A72T (P=0.026) were significantly associated with breastbone length (BBL) in FG. Whereas A57G was significantly associated with chest weight (CW, P=0.004), BBL (P=0.009), and body length (BL, P=0.009) in SV, while A72T was significantly associated with BBL (P=0.014) and BL (P=0.028) in SV. Haplotypes based on these 2 SNPs showed significant effects on BBL in FG strain (P=0.000), and they also had significant effects on CW (P=0.007), BBL (P=0.004), and BL (P=0.001) in SV strain. Additionally, A57G was significantly associated with liver rate (LR) in FG strain (P=0.017). A72T showed significant associations with dressed carcass weight (DCW, P=0.048) and breast muscle weight (BMW, P=0.018) in FG strain. A57G was significantly associated with DCW (P=0.048), whole net carcass weight (WNCW, P=0.048), BMW (P=0.036), and liver muscle rate (LMR, P=0.003) in SV strain. Haplotypes also displayed significant effects on BMW (P=0.029) and LMR (P=0.010) in FG strain. These findings indicated that the IGF-1R gene could serve as a valuable molecular genetic marker for enhancing growth traits and carcass traits in meat-type quails.

Association of Vitamin-D Receptor Gene Single Nucleotide Polymorphism (FokI) with COPD

Background: Vitamin D receptor gene (VDR) polymorphism and its association with various diseases have been previously investigated. But the association of vitamin D receptor gene polymorphism with COPD has not been investigated yet.&#x0D; Objective: To assess the association between vitamin D receptor gene polymorphism (FokI) and COPD.&#x0D; Methods: This cross sectional study was carried out in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from March 2019 to February 2020. For this study, 15 (fifteen) pulmonologists diagnosed COPD patients with age 40 to 80 years (post-bronchodilator FEV1/FVC&lt;0.70 and FEV1&lt;80% predicted) and 15 (fifteen) apparently healthy age-matched individuals (for comparison), were selected. The single nucleotide polymorphism of vitamin D receptor gene (FokI) of all subjects was assessed by PCR-RFLPs. Data were expressed as mean ± SD and percentage. Statistical analysis was done by independent sample ‘t’ test and chi-square test. In the interpretation of the results, ≤0.05 level of probability (p) was accepted as significant.&#x0D; Results: The frequency distribution of FokI genotype was 13.33% (FF), 73.34% (Ff), 13.33% (ff) and 13.33% (FF), 80% (Ff), 6.66% (ff) COPD patients and healthy subjects, respectively. Associations of FokI [FF (OR 1,95% CI 0.12-8.21, p=1.00); Ff (OR 0.68,95% CI 0.12-3.78, p=0.66); ff (OR 2.15,95% CI 0.17-26.67, p=0.54)] VDRSNP with COPD was statistically non-significant. Conclusion: The present study reveals that the FokI of VDR SNP is not associated with COPD.&#x0D; Central Medical College Journal Vol 6 No 1 January 2022 Page: 14-21

The effect of insulin-like growth factor 1 receptor gene single nucleotide polymorphism on growth and milk production traits in two native Indian tropical goat breeds

Insulin like growth factor1(IGF-1) is an essential growth factor that mediates the growth-promoting functions of pituitary growth hormone. Insulin like growth factor 1 receptor (IGF1R) is a tyrosine kinase receptor that mediates the actions of IGF1. Therefore, IGF1R is a candidate gene for examining SNPs linked with growth and production traits. The objective of this study was to detect the c.546 + 179170A > T transversion in intron 2 of the gene encoding IGF1R in two goat breeds, Attappady Black and Malabari, and examine the association of this polymorphism with growth and milk production. For the identification of the SNP, the T-ARMS-PCR was utilized. All three genotypes were present in the two investigated breeds. The polymorphism was found to be significantly (p < 0.05) linked with growth traits. At birth, 3 and 6 months of age, Attappady goats with the AT genotype had significantly (p < 0.05) higher body weights than those with the AA and TT genotypes. Malabari goats with the AT genotype had significantly (p < 0.05) higher body weights at birth and at 3 months of age. The genotypes of the IGF1R gene had no effect on total or peak milk production. Therefore, this SNP could be used as a molecular marker in selection of meat-producing goat breeds. HIGHLIGHTS c.546 + 179170A > T IGF1R transversion was detected using T-ARMS-PCR in two indigenous goat breeds from Kerala. Attappady Black and Malabari goat breeds of Kerala possessed all the three genotypes In these breeds, there was a significant correlation between this SNP, c.546 + 179170A > T IGF1R, and body weight. In both the breeds, there was no association between this SNP and milk production traits.

Plasma 25-Hydroxyvitamin D Level and VDR Gene Single Nucleotide Polymorphism rs2228570 Influence on COVID-19 Susceptibility among the Kazakh Ethnic Group-A Pilot Study.

Low plasma levels of the vitamin D metabolite 25-hydroxyvitamin D [25(OH)D] and the vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) have been associated with the body's susceptibility to infectious diseases, including COVID-19. In this pilot retrospective study, representatives of the Kazakh population (central Kazakhstan) were divided into groups based on the test for IgM and IgG for coronavirus infection. We compared the 25(OH)D plasma levels and concluded that the COVID-19-positive group values (25.17 ng/mL ± 16.65) were statistically lower (p = 0.0114) compared to the COVID-19-negative ones (35.58 ng/mL ± 20.67). There was no association between age, gender and 25(OH)D concentration within the groups (p > 0.05). The genotyping of rs2228570 was performed using a TaqMan Real-Time PCR assay. Allele C predominated among the COVID-19-negative participants and significantly reduced the likelihood of coronavirus infection (p < 0.0001; OR = 0.0804; 95% CI 0.02357-0.2798). There were no statistically significant differences in the frequencies of the A, G and T alleles in the studied groups (p > 0.05). The GG genotype of rs2228570 was associated with a 4.131-fold increased likelihood of COVID-19 infection (p = 0.0288; χ2 = 5.364; OR = 4.131; 95% CI 1.223-13.71). Comprehensive studies are required to determine whether low 25(OH)D plasma concentrations and genetic background represent a risk factor for COVID-19 infection.

Genetic variants of the vitamin D receptor are related to dynapenia in postmenopausal women

BackgroundDynapenia increases with age and in the case of women is possibly influenced by menopause, yet whether vitamin D affects this increase remains controversial. The influence of genetic variants (single nucleotide polymorphisms) of the vitamin D receptor on dynapenia is an understudied area. AimTo analyze the association between genetic variants of the vitamin D receptor gene and dynapenia in a cohort of community-dwelling postmenopausal women. MethodsWe performed a cross-sectional study of 463 women in a university hospital. Grip strength was used as an indicator of dynapenia. Differences in grip strength among single nucleotide polymorphisms rs11568820 and rs2228570 genotypes of the vitamin D receptor gene were assessed after adjusting for confounding variables, and the percentage of phenotypic variance was estimated by linear regression. ResultsDynapenia (grip strength <20 kg) was diagnosed in 178 of the women (38.45 %). A difference in grip strength, corresponding to variants of the vitamin D receptor gene single nucleotide polymorphism rs11568820, was found when using an additive model of inheritance, with lower grip strength for the TT genotype (ANOVA, p = 0.030, close to the 0.025 significance level determined by Bonferroni correction). Assuming a recessive inheritance model for allele T, the between-group difference in grip strength was significant (TT = 19.79 ± 3.10 kg vs. CC/CT = 21.58 ± 3.49 kg, p = 0.008) after adjusting for age, body mass index, comorbidities, and sociodemographic variables. More women with dynapenia had the TT genotype (60.71 %) than the CC or CT genotype (37.01 %) (p = 0.012). ConclusionThis study demonstrates that the TT genotype of the rs11568820 SNP of the vitamin D receptor gene was associated with decreased grip strength in community-dwelling postmenopausal women.

Association of Vitamin D Receptor Gene Single Nucleotide Polymorphism (TaqI) with COPD

Background: Vitamin D receptor gene (VDR) polymorphism and its association with various diseases have been previously investigated. But the association of vitamin D receptor gene polymorphism with COPD has not been investigated yet.&#x0D; Objective: To assess the association between vitamin D receptor gene polymorphism (TaqI) and COPD.&#x0D; Methods: This cross-sectional study was carried out in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, from March 2019 to February 2020. For this study, 15 (fifteen) pulmonologists diagnosed COPD patients with age 40 to 80 years (post-bronchodilator FEV1/FVC &lt;0.70 and FEV1 &lt;80% predicted) and 15 (fifteen) apparently healthy age-matched individuals (for comparison), were selected. The single nucleotide polymorphism of the vitamin D receptor gene (TaqI) of all subjects was assessed by PCR-RFLPs. Data were expressed as mean ± SD and percentage. Statistical analysis was done by independent sample‘t’ test and chi-square test. In the interpretation of the results, ≤ 0.05 level of probability (p) was accepted as significant.&#x0D; Results: The frequency distribution of the TaqI VDR SNP was 0% (TT), 0% (Tt), 100% (tt) and 0% (TT), 0% (Tt), 100% (tt) COPD patients and healthy subjects, respectively. There was no association between TaqI VDR SNP with COPD.&#x0D; Conclusion: The present study reveals that TaqI of VDR SNP is not associated with COPD.&#x0D; EMCJ. July 2022; 7(2): 21-27

Association of vitamin D receptor gene haplotypes with late-onset Alzheimer's disease in a Southeastern European Caucasian population.

Vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) have been investigated over the past years with the aim of identifying any association with the development of Alzheimer's disease (AD). However, information regarding the potential association of VDR SNP haplotypes with AD is limited. The aim of the present study was to provide additional knowledge on the effects of VDR haplotypes on the development of late-onset AD in a cohort of Southeastern European Caucasians (SECs). The study sample included 78 patients with late-onset AD and 103 healthy subjects as the control group. VDR SNPs that were analyzed were TaqI (rs731236), BsmI (rs1544410) and FokI (rs2228570). The CAC (TaqI, BsmI and FokI) haplotype was found to be associated with a 53% lower risk of developing the disease (OR, 0.47; 95% CI, 0.23-0.96; P=0.04) and the TAC (TaqI, BsmI and FokI) haplotype was associated with an ~6-fold greater risk of developing AD (OR, 6.19; 95% CI, 1.91-20.13; P=0.0028). Female subjects carrying the TAC haplotype had a ~9-fold greater risk of developing AD in comparison to female control subjects (OR, 9.27; 95% CI, 1.86-46.28; P<0.05). The TaqI and BsmI polymorphisms were in high linkage disequilibrium (D'=0.9717, r=0.8467) and produced a haplotype with a statistically significant different frequency between the control and AD group. The TA (TaqI and BsmI) haplotype was associated with an ~8-fold greater risk of developing AD (OR, 8.27; 95% CI, 2.70-25.28; P<0.05). Female TA carriers had an ~14-fold greater risk of developing the disease in comparison to female control subjects (OR, 13.93; 95% CI, 2.95-65.87; P<0.05). On the whole, the present study demonstrates that in the SEC population, TAC and TA are risk haplotypes for AD, while the CAC haplotype may act protectively. SEC women carrying the TAC or TA haplotype are at a greater risk of developing AD, thus suggesting that women are markedly affected by the poor utilization of vitamin D induced by the VDR haplotype.

Oxytocin receptor gene, post-traumatic stress disorder and dissociation in a community sample of European American women.

The aims of this study were: (a) to examine associations of oxytocin receptor gene (OXTR) single nucleotide polymorphisms (SNPs) with post-traumatic stress disorder (PTSD) and dissociative symptoms and (b) to investigate gene-environment (G × E) interaction with childhood maltreatment. Salivary DNA samples from 228 women of European ancestry were analysed. Two SNPs, rs237895 and rs237897, were associated with dissociative symptoms but not PTSD diagnosis. Another SNP (rs2254298) was associated with dissociation when interacting with history of childhood maltreatment. These results contribute to theorising and evidence suggesting that the oxytocin system and its genetics may be associated with risk for dissociation among European American women, including those with maltreatment history. Replication with larger patient samples, including men and other ancestry groups, is needed.

Vitamin D receptor gene polymorphism influence on lumbar intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration is a multifaceted pathology that is the main morphological cause of lower back pain. This study aimed to determine the link between the vitamin D receptor gene single nucleotide polymorphisms (SNPs) and degenerative processes of the lumbar spine. The complete lumbar spinal columns were collected from 100 Caucasian cadavers via ventral dissection. The specimens for the histological analysis were harvested from the L5/S1 IVDs and endplates. Then, the tissues were cut into slices, inserted into paraffin blocks, and stained. The histology was evaluated according to the Boos' protocol. Moreover, TaqI(rs731236), FokI(rs2228570), and ApaI(rs7975232) genotyping were performed. Lastly, the histological scores for different genotypes were analyzed. The overall Boos' score in the study group was 12.49. It consisted of a mean IVD score of 7.46 and endplate score of 5.39. The determination of the SNPs was successful in 99 specimens and had a distribution of all alleles in accordance with the Hardy-Weinberg equilibrium. No significant differences in overall histological degeneration scores were found between samples from donors with different genotypes. However, in subgroup analysis of specific regions on the IVD, the significant difference was found in posterior inner anulus fibrosus for ApaI. The results of this study suggest that one must be careful when interpreting the results of the clinical and/or radiological studies on vitamin D receptor gene polymorphisms and lumbar spine degeneration risk, because such a relationship, if present, is likely to be very subtle.

NR3C1 Glucocorticoid Receptor Gene Polymorphisms Are Associated with Membranous and IgA Nephropathies.

Glomerular diseases (GNs) are responsible for approximately 20% of chronic kidney diseases. Glucocorticoid receptor gene (NR3C1) single nucleotide polymorphisms (SNPs) are implicated in differences in predisposition to autoimmunity and steroid sensitivity. The aim of this study was to evaluate the frequency of the NR3C1 SNPs—rs6198, rs41423247 and rs17209237—in 72 IgA nephropathy (IgAN) and 38 membranous nephropathy (MN) patients compared to 175 healthy controls and to correlate the effectiveness of treatment in IgAN and MN groups defined as a reduction of proteinuria <1 g/24 h after 12 months of treatment. Real-time polymerase chain reactions and SNP array-based typing were used. We found significant rs41423247 association with MN (p = 0.026); a significant association of rs17209237 with eGFR reduction after follow-up period in all patients with GNs (p = 0.021) and with the degree of proteinuria after 1 year of therapy in all patients with a glomerulopathy (p = 0.013) and IgAN (p = 0.021); and in the same groups treated with steroids (p = 0.021; p = 0.012). We also observed the association between rs41423247 and IgAN histopathologic findings (p = 0.012). In conclusion, our results indicate that NR3C1 polymorphisms may influence treatment susceptibility and clinical outcome in IgAN and MN.

The Impact of Luteinizing Hormone/Chorionic Gonadotropin Hormone Receptor Gene Polymorphism rs68073206 in Men with Non-obstructive Azoospermia: A Case-control Study

Background: The functional consequences of the luteinizing hormone/chorionic gonadotropin hormone receptor (LHCGR) gene single nucleotide polymorphism (rs68073206) on male infertility in patients with non-obstructive azoospermia (NOA) is not clear.&#x0D; Objective: To examine whether the presence of LHCGR gene; rs68073206 single nucleotide polymorphisms (SNPs) can be associated with incidence of non-obstructive azoospermia.&#x0D; Materials and methods: A case-control study comprised of a total of 70 unrelated Iraqi infertile men with non-obstructive azoospermia (zero sperm in semen) whose were on two groups: Group I that were diagnosed to have NOA but didn’t receive infertility treatment yet (33 patient with age of 31.58±1.059 year) and group II that were receiving injectable gonadotropin treatment (37 patient with age of 33.46±1.173 year). In addition to 34 age and BMI matched healthy fertile normozoospermic men (according to the parameters of WHO, 2010). The study population was genotyped by TaqMan assay for LHCGR gene single nucleotide polymorphism (rs68073206). The level of each hormone was estimated by immunoassay technique while the sperm analyses were conducted in accordance with the World Health Organization criteria.&#x0D; Results: The study revealed a statistically significant higher hormonal level of serum inhibin B in infertile group I patients with wild GG genotype (246.445±224.106 pg/ml), and the p-value is (0.0439) as compared to that hormone levels of GT and TT genotypes carriers that were (85.969±71.685 pg/ml) and (56.420±23.988 pg/ml) respectively. ). The genotyping variations of patients, whether carrying the homozygous GG, heterozygous GT or homozygous TT genotype, did not reveal a statistically significant difference in distribution as compared to control individuals.&#x0D; Conclusions: The LHCGR gene rs68073206 polymorphisms in our population having non-obstructive azoospermia can be suggested to have a modulating potential in variable gonadotropin sensitivity. The detected non-significant difference in genotypic prevalence can be attributable to the limited sample size.

Association of Vitamin D and its Receptor (VDR) Gene Single Nucleotide Polymorphism (ApaI and TaqI) with Risk of Psoriasis

Introduction: Psoriasis is one of the skin related inflammatory diseases that affects a low percentage of population around the globe. Vitamin D through Vitamin D Receptor (VDR) also regulates the function of white blood cells in psoriasis. Mutations in VDR gene have shown abnormalities in immune responses like psoriatic arthritis. To determine the possible association between Vitamin D Receptor (ApaI and TaqI) gene polymorphism and psoriasis, a case-control study was designed and conducted at the Institute of Basic Medical Sciences (IBMS), Khyber Medical University (KMU) Peshawar and health units of Peshawar. Method: This multi-centre study included 220 samples (110 cases of psoriatic disease and 110 healthy controls). DNA was extracted using modified salting out protocol. VDR gene polymorphisms (TaqI and ApaI) were genotyped using amplification refractory mutation system using polymerase chain reaction (ARMSPCR) method. Results were statistically analyzed. Result: Our study showed significant association between VDR gene (TaqI, ApaI) polymorphisms and psoriasis with p-value of 0.009 (0.0019 and 0.0162) and odds ratios (95% confidence interval) for psoriasis of CC vs CT (TaqI) and AA vs AC (ApaI) were 2.963 (95% CI: 1.508-5.743) and 2.293 (95% CI:1.22-4.246) respectively. Conclusion: Findings indicate that VDR gene polymorphisms (TaqI, ApaI) are significantly associated with onset and progression of psoriasis, and mutations in these loci are risk factors for development of psoriasis. Key words: Psoriasis, VDR polymorphism, TaqI, ApaI, South Asia, Pakistan

The role of oxytocin signaling in depression and suicidality in returning war veterans

Many war veterans struggle with depression and suicidality, and separation from the military is a time of particularly high risk. Based on research in non-human animals, we hypothesized that reduced oxytocin signaling would mediate symptoms of depression and suicidality in war veterans recently separated from their close comrades. We also hypothesized that veterans with more frequent contact with comrades would have fewer symptoms of depression and suicidality. In this cross-sectional study, male veterans from the Iraq and Afghanistan wars (n = 86) provided blood and urine samples for measurement of peripheral oxytocin (OT) levels, as well as saliva samples for DNA extraction followed by genotyping of oxytocin receptor gene (OXTR) Single Nucleotide Polymorphisms, and CpG-methylation assessment. Participants also completed a series of mental health questionnaires and interviews. Veterans reported feeling very close to their comrades during war, and missing them greatly upon returning home. Neither peripheral OT levels nor OXTR genotypes were related to symptoms of depression or suicidality. On the other hand, methylation at OXTR CpG −924 was negatively correlated with depressive symptomology, after controlling for possible confounds. Veterans who socialized with comrades more frequently had higher levels of urinary, but not plasma OT, as well as less depressive symptomology. Social connectedness was a strong negative predictor of symptoms of both depression and suicidality, eclipsing the predictive power of other variables such as post-deployment social support, the degree to which participants reported missing their comrades, and the frequency with which they socialized with comrades. Our results suggest that veteran mental health is more impacted by lack of social connectedness than by separation from close comrades per se. While there is some evidence that OXTR methylation relates to depressive symptomology, decreased OT signaling does not appear to mediate the relationship between social disconnectedness and depression or suicidality. Sleep quality and anxiety disorders were also significantly associated with mental health symptoms, independent of social connectedness. Our findings suggest that efforts aimed at alleviating the burden of depression and suicidality in returning war veterans should focus on re-integrating veterans into society and establishing a feeling of social connectedness, as well as on treating anxiety disorders and sleep problems.

Vitamin D Receptor Gene Single Nucleotide Polymorphisms and Association With Vitamin D Levels and Endoscopic Disease Activity in Inflammatory Bowel Disease Patients: A Pilot Study.

Inflammatory bowel diseases (IBDs) comprise a heterogenous group of chronic gastrointestinal disorders that are multifactorial in etiology. Experimental in vitro and in vivo studies suggest that intestinal vitamin D receptor (VDR) signaling plays a role in modulating the immune response in IBD as a cause and/or a consequence of chronic inflammation. The aim of this study is to study the associations between vitamin D receptor gene single nucleotide polymorphisms(SNPs), vitamin D levels, and endoscopic disease activity in IBD. This is a cross-sectional analysis of IBD patients who underwent endoscopic evaluation at a tertiary care hospital. Demographic variables, IBD disease type and location, medical therapies, vitamin D levels, and endoscopic disease activity were collected. Colonic biopsies obtained were investigated for the presence of VDR SNPs: ApaI, TaqI, BsmI, FokI, and Tru9I. Patients in endoscopic remission had higher vitamin D levels compared with those with inflammation found on endoscopy (P = <0.001). Patients with lower vitamin D levels were homozygous for Fok ancestral alleles (P = 0.0045). With regard to endoscopic disease activity, we found no differences in mutations of any of the VDR SNPs in our sample. The association between the presence of the ancestral FokI and lower vitamin D levels suggests a multifactorial etiology for vitamin D deficiency in IBD. Higher vitamin D levels in those in endoscopic remission compared with lower levels in those with active inflammation suggests that the impact of VDR gene SNP on disease activity may be overcome with replacement therapy.

Follicle-stimulating hormone receptor gene polymorphisms of ovarian reserve markers in Romanian population.

Association between phenotype and follicle-stimulating hormone (FSH) receptor and FSH beta chain genotype was evaluated in women with ovarian dysfunction. FSH receptor gene single nucleotide polymorphisms (SNPs) were analyzed by restricted fragment length polymorphism (RFLP) technique. Three groups were analyzed: two groups formed of poor responders (women with ovarian dysfunctions caused by endometriosis and patients who underwent ovarian stimulation protocols) and a third good responders group (normal-ovulatory women who gave birth to naturally conceived children). A higher average level of basal FSH values were found in mutants in the A919G/Ala307Thr/rs6165 or A2039G/Asn680Ser/rs6166 tests (7.16±1.09; P=0.659). Anti-mullerian hormone (AMH) below 1.2 ng/ml was associated with a higher frequency of mutations: 33.3% A919G/Ala307Thr and A2039G/Asn680Ser (P=0.137) and also in 66.6% FSH receptor less frequent polymorphism (c.-29G>A) rs 1394205 (P=0.522). The age, day 3 FSH, and AMH levels are widely used to investigate female infertility. However, we have not yet found the ideal biomarker to determine the best outcome and treatment plan for our patients. We cconsider that genetic markers will become the future in the personalization of controlled ovarian stimulation treatment in the upcoming period.

The MC4R SNPs, their haplotypes and gene-environment interactions on the risk of obesity

BackgroundLittle is known about the correlation between the melanocortin 4 receptor gene (MC4R) single nucleotide polymorphisms (SNPs) and the risk of obesity. This research sought to test the MC4R rs17782313, rs476828 and rs12970134 SNPs, their haplotypes and gene-environment interactions on the risk of obesity in the Maonan ethnic group, an isolated minority in China.MethodsA case-control study comprised of 1836 participants (obesity group, 858; and control group, 978) was conducted. Genotypes of the three SNPs were determined by the next-generation sequencing (NGS) technology.ResultsThe genotypic frequencies of the three SNPs were different between the obesity and control groups (P < 0.05 for all). The minor allelic frequency of the MC4R rs17782313C, rs476828C and rs12970134A was higher in obesity than in control groups (13.8% vs. 8.3%, P < 0.001, 17.1% vs. 10.9%, P < 0.001; and 15.5% vs. 11.5%, P < 0.001; respectively). Additionally, the dominant model of rs17782313 and rs476828 SNPs revealed an increased morbidity function on the risk of obesity (P < 0.05). A correlation between SNP-environment and the risk of obesity was also observed. The rs17782313C-rs476828C-rs12970134A haplotype was associated with high risk of obesity (OR = 1.796, 95% CI = 1.447–2.229), whereas the rs17782313T-rs476828T-rs12970134G and rs17782313T-rs476828T-rs12970134A haplotypes were associated with low risk of obesity (OR = 0.699, 95% CI = 0.586–0.834 and OR = 0.620, 95% CI = 0.416–0.925; respectively). The interactions between haplotype and waist circumference on the risk of obesity were also noted.ConclusionsWe discovered that the MC4R rs17782313, rs476828 and rs12970134 SNPs and their haplotypes were associated with the risk of obesity in the Chinese Maonan population.

The 2039 A/G FSH receptor gene polymorphism influences glucose metabolism in healthy men

ObjectiveTo assess the role of c. 2039 A/G (p. Asp680Ser) (rs6166) and c. −29 G/A (rs1394205) follicle-stimulating hormone receptor (FSHR) gene single nucleotide polymorphisms (SNPs) in a cohort of healthy men.MethodsOne-hundred twenty-seven healthy men underwent evaluation of the anthropometric parameters, assessment of metabolic and lipid profile, measurement FSH serum levels, and genotyping of both the aforementioned FSHR SNPs. Data grouped according to the FSHR rs6166 or rs1394205 genotypes underwent to statistical analysis.Main resultsThe three groups of men for each FSHR SNP did not differ statistically significantly for body mass index and serum FSH levels. As for FSHR rs6166 SNP, glucose levels were significantly lower in men with the GG genotype compared with those with the AA genotype. Men with AG had lower insulin levels and HOMA index values compared with those carrying the genotype AA (p < 0.05). The GG group showed a negative correlation between serum FSH levels and insulin and between serum FSH levels and HOMA index (p < 0.05). In contrast, men grouped according to the FSHR rs1394205 genotype showed no significant difference in blood glucose, serum insulin levels, and HOMA index. The AG group showed a negative correlation between FSH insulin and between serum FSH levels and HOMA index (p < 0.05).ConclusionsMen with the genotype GG of the FSHR rs6166 SNP have lower blood glucose levels than those with the AA genotype. Their FSH levels inversely correlated with insulin and HOMA index. In contrast, the genotype FSHR rs6166 A/G did not reveal any role of FSH on glucose metabolism in healthy men. The inverse relationship between FSH and insulin or HOMA index in the group with the genotype GG of the FSHR rs6166 SNP suggests a possible cross-talk between FSH and insulin.

Reproductive hormones during pubertal transition in girls with transient Thelarche

Transient thelarche (TT), that is, the appearance, regression and subsequent reappearance of breast buds, is a frequent phenomenon, but little is known about pubertal transition in these girls. To describe pubertal progression, growth, genotypes, reproductive hormones and growth factors in girls with TT compared to those who do not present TT (non-TT). Retrospective analysis of a longitudinal population-based study. Girls (n=508) of the Chilean Growth and Obesity cohort. Pubertal progression, reproductive hormones, follicle stimulating hormone (FSH) beta subunit/FSH receptor gene single nucleotide polymorphisms and growth. Thirty-seven girls (7.3%) were presented TT. These girls entered puberty by pubarche more frequently (51%) than girls with normal progression (non-TT; n=471; 23%, P=.005). Girls with TT who were under 8years old had lower androgens, anti-Müllerian hormone (AMH), luteinizing hormone (LH) and oestradiol (all P<.05) than older girls with TT. At the time of Tanner breast stage 2 (B2), girls with TT had higher androgens, LH, FSH, IGF1, LH, insulin and oestradiol (P<.01) than at the time of TT. TT girls were older at B2 (10.3±1.1 vs. 9.2±1.2years, P<.001) and menarche (12.3±0.8 vs. 12.0±1.0years, P=.040) than their counterparts (non-TT). No differences in anthropometric variables or FSHB/FSHR genotypes were detected. Transient thelarche is a frequent phenomenon that does not appear to be mediated by hypothalamic-pituitary-gonadal axis activation or by adiposity. Hormonal differences between earlier TT and later TT suggest that their mechanisms are different.