Receptor Gene Variants Research Articles

Interest and Utility of MC1R Testing for Melanoma Risk in Dermatology Patients with a History of Nonmelanoma Skin Cancer.

Public access to genetic information is increasing, and community dermatologists may progressively encounter patients interested in genetic testing for melanoma risk. Clarifying potential utility will help plan for this inevitability. We determined interest and uptake of genetic risk feedback based on melanocortin receptor gene (MC1R) variants, immediate (two weeks) responses to risk feedback, and test utility at three months in patients (age ≥ 18, with a history of nonmelanoma skin cancer). Participants (N = 50) completed a baseline survey and were invited to consider MC1R testing via the study website. Testing interest and uptake were assessed through registration of test decision, request of a saliva test kit, and kit return (all yes/no). Immediate responses to risk feedback included feedback-relevant thoughts, emotions, communication, and information seeking after result receipt; test utility outcomes included family and physician communication and information seeking. Results indicated good retention at both time points (76%; 74%). Half (48%) logged onto the study website, and of these, most (92%) chose testing and (95%) returned a saliva sample. After two weeks, most (94%) had read all the risk feedback information and distress was low (M = 8.81, 7–28, SD = 2.23). Many (69%) had talked with their family about the results. By three months, most had spoken with family (92%) and physicians (80%) about skin cancer risk. Physician communication was higher (70%) in those tested versus those not tested (40%, p = 0.02). The substantial interest and promising outcomes associated with MC1R genetic testing in dermatology patients inform intervention strategies to enhance benefits and minimize risks of skin cancer genetic testing.

Variation in TAS2R receptor genes explains differential bitterness of two common antibiotics.

For pharmaceuticals to deliver their full benefits with maximum efficacy, patients need to follow recommended dosing schedules, in terms of amount and frequency. Unfortunately, the aversive taste of many drugs, especially bitterness, can reduce patient compliance in oral liquid formulations. Given common genetic differences in bitter taste receptor genes (TAS2Rs), some individuals may be at increased risk for poor compliance due to heightened bitterness that becomes a barrier to proper use. Here we report on the sensory profile of two antibiotics, chloramphenicol and ofloxacin, investigating whether bitterness intensity associates with nominally functional TAS2R variants. Participants (n = 143) rated suprathreshold intensity on a general Labeled Magnitude Scale (gLMS) for chloramphenicol and ofloxacin; propylthiouracil (PROP) was included as a control, given robust prior associations with TAS2R38 variants. The dominant sensation from chloramphenicol and ofloxacin was bitterness, falling just below “moderate” on a gLMS. TAS2R38 diplotype associated with variable bitterness of chloramphenicol and PROP, but not ofloxacin. The bitterness of ofloxacin associated with a TAS2R9 SNP (V187A). This pilot study provides novel evidence on differences in the bitterness from two antibiotics, which are associated with TAS2R variants. Improved understanding of individualized barriers to patient compliance, especially for oral formulations, can guide future efforts to optimize delivery systems for improved compliance.

The vitamin D receptor gene variants, ApaI, TaqI, BsmI, and FokI in diabetic foot ulcer and their association with oxidative stress.

To date, numerous disorders have been linked to vitamin D deficiency. Several lines of evidence indicate a relationship between vitamin D deficiency and the risk of developing type 2 diabetes. It has been postulated that vitamin D may influence insulin activity, which can predispose individuals to develop type 2 diabetes. In this case-control study, 262 patients with definite type 2 diabetes were enrolled, considering whether they were being affected by diabetic foot ulcers or not. The plasma levels of vitamin D and homocysteine were measured using ELISA, and the PCR-RFLP technique was utilized to determine allele and genotype frequencies. The antioxidant capacity of plasma samples of diabetic patients was analyzed using the thiobarbituric acid reactive substance (TBARS) and ferric reducing ability of plasma (FRAP) assays. The obtained results demonstrated no significant difference in the frequency of TaqI and BsmI polymorphisms between the case and control groups. However, the frequency of genotypes and alleles of the ApaI polymorphism in the VDR gene significantly differed between the case and control groups. A significant correlation was found between ApaI polymorphism and oxidative stress, as patients with the GG genotype had lower levels of TBARS than those with other genotypes. Furthermore, in the case group, patients with the CC genotype of BsmI showed a significant decrease in TBARS levels. It seems that the plasma levels of vitamin D do not differ between patients with or without diabetic foot ulcers; however, the presence of some VDR gene polymorphisms is thought to be involved in the development of diabetic foot ulcers via increasing oxidative stress.

Correlations of Gene Variants LEP <i>rs2167270</i>, LEPR <i>rs1137100</i>, GHRL <i>rs696217</i>, <i>rs27647</i>, and NPY <i>rs16147</i> with Obesity and Adolescent Eating Behavior: Case-Control Study

Background. Childhood obesity is topical global healthcare issue. The correlations between variable regions of genes encoding leptin and its receptor, ghrelin and neuropeptide Y, and the risk of obesity development in children have not been confirmed completely. Mechanisms for implementing such correlation via the influence of genes on children’s behavior remain unexplored.Objective. The aim of the study is to examine the correlation between leptin, leptin receptor, ghrelin and neuropeptide Y gene variants and obesity in adolescents and their eating behavior.Methods. The study included children aged from 10 to 18 years with exogenous constitutive obesity and normal body weight. Variants in genes for leptin LEP rs2167270, leptin receptor LEPR rs1137100, ghrelin GHRL rs696217 and rs27647, neuropeptide Y NPY rs16147 were determined. Adolescents’ eating behavior was evaluated via psychometric questionnaires DEBQ (Dutch Eating Behavior Questionnaire) and TFEQ (the Three Factor Eating Questionnaire).Results. Gene variant distribution analysis in 150 obese and 150 normal weight children has revealed correlation with obesity for the variant rs1137100 of the LEPR gene (p = 0.001). Variants rs2167270 of the LEP gene (p = 0.015), rs696217 of the GHRL gene (p = 0.040), and rs16147 of the NPY gene (p = 0.020) were associated with adolescent eating behavior predisposing to obesity.Conclusion. The leptin receptor gene variant rs1137100 is associated with obesity in adolescents, and the variants rs2167270 of the leptin gene, rs696217 of the ghrelin gene, and rs16147 of the neuropeptide Y gene are associated with changes in eating behavior.

Leveraging an existing whole-genome resequencing population data set to characterize toll-like receptor gene diversity in a threatened bird.

Species recovery programs are increasingly using genomic data to measure neutral genetic diversity and calculate metrics like relatedness. While these measures can inform conservation management, determining the mechanisms underlying inbreeding depression requires information about functional genes associated with adaptive or maladaptive traits. Toll‐like receptors (TLRs) are one family of functional genes, which play a crucial role in recognition of pathogens and activation of the immune system. Previously, these genes have been analysed using species‐specific primers and PCR. Here, we leverage an existing short‐read reference genome, whole‐genome resequencing population data set, and bioinformatic tools to characterize TLR gene diversity in captive and wild tchūriwat’/tūturuatu/shore plover (Thinornis novaeseelandiae), a threatened bird endemic to Aotearoa New Zealand. Our results show that TLR gene diversity in tchūriwat’/tūturuatu is low, and forms two distinct captive and wild genetic clusters. The bioinformatic approach presented here has broad applicability to other threatened species with existing genomic resources in Aotearoa New Zealand and beyond.

Relationship between a near Melanocortin-4 receptor gene variant and puberty timing in children is vague unlike obesity.

Obesity is a complicated phenomenon which is a combination of genetic, environmental, and psychological factors. Genetic factors of obesity play an important role in individual risk. It is well known that obese children have disturbed puberty timing. To the best of our knowledge, no study has been performed to investigate the association between MC4R gene mutation and puberty timing. This study was performed as a cross-sectional study evaluating the near MC4R rs17782313 variation in 60 obese children and 98 healthy non obese children. Weight, height, BMI ( Body Mass Index ), BMI z-score (BMIz), family history of diabetes mellitus and obesity, the age of the obesity onset, overeating behavior, type of obesity (central or general) and puberty stage were evaluated in 60 obese children. The average age of the participants was 14.87 (+/- 1.3) years, with average weight and BMI of 90.77 (+/-12.2) Kg and 31.72 (+/-4.35) Kg/m2, respectively. Compared to healthy non obese patients, those with C-T genotype (C-T Vs. T-T and C-C) had higher odds of obesity than those with T-T and C-C genotype (p < 0.0001) while genotype TT showed significant protective effect (p = 0.0007). The heterozygote individuals (CT) have a higher BMIz than homozygote ones (CC and TT) (2.8 vs. 2.5 Kg/m2, p = 0.04). children with CT genotype have 5.1 increased risk of obesity. While genotype TT showed significant obesity protective effect. We did not find association of this polymorphism with either childhood eating disorders or puberty. It is recommended to perform a cohort study in a larger sample. The online version contains supplementary material available at 10.1007/s40200-022-01011-5.

Differential distribution of vitamin D receptor (VDR) gene variants and its expression in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disorder that displays an important genetic background. Vitamin D3 (VD3 ) through its receptor (VDR) plays an important immunomodulatory role in autoimmune misbalance, being capable of modulating immune responses. Genetic alterations in VDR gene may contribute to an altered risk in SLE development and clinical manifestations. We investigated VDR SNPs (single nucleotide polymorphisms) frequencies in 128 SLE patients and 138 healthy controls (HC) and mRNA differential expression in 29 patients and 17 HC regarding SLE susceptibility as well as clinical features. We observed that rs11168268 G allele (OR=1.55, p=.01) and G/G genotype (OR=2.69, p=.008) were associated with increased SLE susceptibility. The rs2248098 G allele and A/G and G/G genotypes were associated to lower SLE susceptibility (OR=0.66, p=.01; OR=0.46, p=.01; OR=0.44, p=.02, respectively). Regarding clinical features, we observed lower risk for: rs11168268 A/G genotype and nephritis (OR=0.31, p=.01); rs4760648 T/T genotype and photosensitivity (OR=0.24, p=.02); rs1540339 T/T genotype and antibody anti-dsDNA (OR=0.19, p=.015); rs3890733 T/T genotype and serositis (OR=0.10, p=.01). We identified a significant downregulation in VDR expression levels when compared patients and controls overall (p=1.04e-7 ), in Cdx-2 A/G and G/G (p=.008 and p=.014, respectively) and in patients with nephritis (p=.016) Our results suggested that VDR SNPs influence upon SLE susceptibility and in particular clinical features, acting on mRNA expression in SLE patients overall and the ones with nephritis.

Vitamin D receptor gene variations and their haplotypic association: Possible impact on gastric cancer risk.

Vitamin D receptor (VDR) gene alterations have been associated with the occurrence and prognosis of various types of cancers, but only few studies have focussed on gastric cancer (GC) risk. This case-control study was conceived to evaluate possible association of VDR polymorphisms (Fok1, Taq1, and Cdx2) with GC risk. A total of 293 subjects, including 143 GC patients and 150 controls were included in this study. The genotypes were elucidated by polymerase chain reaction-restriction fragment length polymorphism followed by DNA sequencing. The frequency of Fok1 genotypes (TC and TT) was found higher in GC cases compared to controls (P ≤ 0.05). In the stratified analysis, we observed a significant association of the (CT + TT) variant with GC risk in males, rural dwellers, smokers, and preobese cases, and those having no family history of Gastrointestinal cancer (P ≤ 0.05). In silico analysis predicted that the Fok1 variant impacts the stability and functional efficiency of the protein. Some exact haplotypes (CCG and CCA) of the VDR gene may act as low penetrance alleles in inclination to GC. VDR Fok1 polymorphism is significantly associated with GC risk in the Kashmiri population. Specific haplotypes in the VDR gene could act synergistically in the development of GC.

Role of Taste Receptor Gene Variations (SNPs) on Diet Quality in Adolescent Females

The prevalence of pediatric obesity has increased over the past 40 years and the rate in females 6 to 19 years old is currently over 19%. This profound increase in obesity is predicted to negatively impact health and result in multiple obesity‐related comorbidities in adulthood. Obesity disproportionately affects ethnic minorities with a higher percentage of adolescent African‐American females (~29%) with obesity compared to non‐Hispanic, white females (~15%). The overconsumption of highly palatable, energy dense, foods are linked to obesity and single nucleotide polymorphisms (SNP) from taste genes are linked to alterations in taste perception and food choices. SNPs are associated with higher rates of obesity and altered fat perception (CD36; fat), higher caloric intake from sugar (TAS1R2; sweet) and increased energy intake (TAS2R38, bitter). An enhanced understanding of genetic, environmental, and behavioral factors contributing to excess weight in adolescents is paramount. Therefore, the goal of the current study was to investigate the intersection of genotype (rs1761667 of CD36 (AA), rs35874116 of TAS1R2 (TT) and rs713598 of TAS2R38 (CC)) and phenotype on diet intake and quality in adolescent African‐American and white females. Genotype was determined by allelic discrimination assay in females (10‐16 years old; n=142) enrolled in the Translational Investigation of Growth and Everyday Routines in Kids (TIGER Kids) Study. Anthropometrics and 24‐hour dietary recalls were conducted for each participant and Healthy Eating Index (HEI) scores, a measure of diet quality, were calculated. The effect of race and genetic variation was assessed using a two‐way ANOVA. Based on allelic discrimination assays, the expression rates of CD36 AA, TAS1R2 TT and TAS2R38 CC in white females (27.7%, 45.0%, 38.3%, respectively) and African‐American females (15.3%, 37.3%, 31.0%, respectively) were determined. Preliminary results indicated that BMI percentiles were higher in African‐American females across all genotypes (p&lt;.05) and moderately affected by TAS2R38 genotype (p&lt;.06). CD36 and race differentially affected HEI for added sugar, total vegetable, greens and beans, whole grain, seafood and plant protein and total HEI, (p&lt;.05). TAS1R2 and race differentially affected HEI‐added sugar (p&lt;.05). TAS2R38 significantly affected HEI‐sodium and total protein (p&lt;.05) and TAS2R38 and race differentially affected HEI for total vegetables, fruits, and whole fruits (p&lt;.09). Fat and sugar intake (g) were positively correlated with SNPs previously associated with altered fat perception (CD36 AA), sugar intake (TAS1R2 TT) and overall energy intake (TAS2R39 CC) in white (p&lt;.05), but not African‐American females, suggesting that the effects of taste receptor SNPs on the relationship between fat and sugar intake differs by race. Overall, the results from these analyses support the intersection between race and genetic variation on HEI, and suggest that SNPs in taste receptor genes differently affect diet quality in adolescent females. Further understanding of the role of taste receptor SNPs on food choices and diet quality is needed to better tailor dietary interventions in the pediatric population.

Allelic Polymorphisms of Killer Immunoglobulin-Like Receptor Genes in Malay and Orang Asli Populations of Peninsular Malaysia

Next-generation DNA sequencing (NGS) technology advancements provide new insight into the level of variation in killer immunoglobulin-like receptor (KIR) genes. High resolution allele genotyping of seven KIR genes was conducted among 94 unrelated Malay and Orang Asli (OA) individuals of Peninsular Malaysia. A manual bioinformatics analysis is performed and optimised by Sanger sequencing method. The Malays expressed a total of 22 alleles, as compared to only 15 alleles in the OA population. In total, 12 centromeric and 9 telomeric allelic haplotypes were identified in the Malays, whereas 8 centromeric and 5 telomeric allelic haplotypes were identified in the OA. The KIR2DL1, KIR2DL3, and KIR2DS4 genes exhibited a high degree of variation and balanced distribution in the Malay and OA populations. On the other hand, KIR2DL4, KIR3DL1, KIR3DL2 and KIR3DL3 genes exhibited a high degree of conservation, with less number of alleles identified and the dominance of a single allele at high frequency. High-resolution KIR allele genotyping has revealed unique sequence variations and allelic haplotypes between individuals and populations. The distributions of KIR alleles and haplotypes are useful for genetic population studies and serve as a baseline for future transplantation matching and disease association research.

Obez ve sağlıklı çocuklarda leptin ve leptin reseptör gen polimorfizmleri

Purpose: The of this study is to explore the differences between leptin (LEPG2548A), which is considered efficacious in respect of adiposity and leptin receptor gene variants (LEPRQ223R, K109R, K656N). Furthermore, the relationship between these differences and the serum leptin level shall be scrutinized. Materials and Methods: A total of 300 volunteers (12-17 years of age) joined our study (150controls–150obese). Blood samples obtained from these individuals were used for DNA isolation. An examination was carried out in order to show polymorphisms of the leptin receptor gene increased by RealTime PCR previously. The variations of the leptin gene were ascertained by implementation of restriction fragment length polymorphism method. Results: Genotype dispersion calculations led to the understanding that the AA-genotype was lower in the K109R polymorphism control group than in the patient group, whereas AG-genotype was higher. The control group of Q223R polymorphism had higher AA-genotype values than the patient group, whereas it showed lower AG-genotype values. Moreover, anthropometric and metabolic results were found to be significantly higher (p in the patient group than in the control group.Conclusion: The patient group of LEPRQ223R polymorphism showed lower AA-genotype values, a higher AG-genotype dispersion and a higher allele-G value. Therefore, a relationship to adiposity has been assumed.

Vitamin D Receptor and Binding Protein Gene Variants in Patients with Essential Tremor.

Several studies have shown an association between some variants in the vitamin D receptor (VDR) and the GC vitamin D binding protein (GC) genes with the risk for Parkinson's disease or other neurological disorders. VDR rs2228570 has shown an association with essential tremor (ET) in a previous study. The aim of this study is to look for the association between several common variants in these genes and the risk for ET. We genotyped 272 patients diagnosed with familial ET and 272 age-matched controls using specific TaqMan assays for VDR rs2228570, VDR rs731236, VDR rs7975232, VDR rs739837, VDR rs78783628, GC rs7041, and GC rs4588 single nucleotide variants (SNVs). We found an association between GC rs7041 SNV and ET using recessive, codominant, and allelic models. Despite our results did not find an association between VDR rs2228570 and ET, the pooled data with those by a previous report suggest this association under recessive, codominant, and allelic models. None of the SNVs studied was related to the age at onset of tremor in ET patients. Data from the current study suggest an association between GC rs7041 and VDR rs2228570 SNVs and ET risk.

Association of leptin and leptin receptor genes variants and pulmonary tuberculosis susceptibility, clinical manifestations in a Chinese population

BackgroundThe aim of our study was to investigate the association of leptin (LEP) gene (rs11761556, rs12706832, rs2167270), leptin receptor (LEPR) gene (rs1137100, rs1137101, rs1805096) variants and pulmonary tuberculosis (PTB) susceptibility, as well as their several clinical manifestations, in a Chinese population. MethodsThis study included a cohort of 489 PTB patients and 489 healthy controls, and six SNPs were genotyped by improved multiple ligase detection reaction (iMLDR). ResultsWe found that there were no significant differences regarding the allele and genotype frequencies of LEP rs11761556, rs12706832, rs2167270, LEPR rs1137100, rs1137101, rs1805096 between PTB patients and healthy controls (all P > 0.05), as well as the results of the dominant model and recessive model (all P > 0.05). In the LEP gene, the rs11761556 AA genotype frequency was significantly associated with the development of fever and pulmonary infection in PTB patients (P = 0.035, P = 0.049). In addition, the relation between main haplotypes and PTB patients was also analyzed, but only haplotype CAG in LEP was significantly associated with PTB susceptibility (P = 0.012). ConclusionsLEP and LEPR heritable variation were not contribute to the pathogenesis of PTB in Chinese. While rs11761556 variant might associate with several clinical features of PTB.

Functional Assessment of Calcium-Sensing Receptor Variants Confirms Familial Hypocalciuric Hypercalcemia.

ContextIn the clinic it is important to differentiate primary hyperparathyroidism (PHPT) from the more benign, inherited disorder, familial hypocalciuric hypercalcemia (FHH). Since the conditions may sometimes overlap biochemically, identification of calcium-sensing receptor (CASR) gene variants causative of FHH (but not PHPT) is the most decisive diagnostic aid. When novel variants are identified, bioinformatics and functional assessment are required to establish pathogenicity.ObjectiveWe identified 3 novel CASR transmembrane domain missense variants, Thr699Asn, Arg701Gly, and Thr808Pro, in 3 probands provisionally diagnosed with FHH and examined the variants using bioinformatics and functional analysis.MethodsBioinformatics assessment utilized wANNOVAR software. For functional characterization, each variant was cloned into a mammalian expression vector; wild-type and variant receptors were transfected into HEK293 cells, and their expression and cellular localization were assessed by Western blotting and confocal immunofluorescence, respectively. Receptor activation in HEK293 cells was determined using an IP-One ELISA assay following stimulation with Ca++ ions.ResultsBioinformatics analysis of the variants was unable to definitively assign pathogenicity. Compared with wild-type receptor, all variants demonstrated impaired expression of mature receptor reaching the cell surface and diminished activation at physiologically relevant Ca++ concentrations.ConclusionThree CASR missense variants identified in probands provisionally diagnosed with FHH result in receptor inactivation and are therefore likely causative of FHH. Inactivation may be due to inadequate processing/trafficking of mature receptor and/or conformational changes induced by the variants affecting receptor signaling. This study demonstrates the value of functional studies in assessing genetic variants identified in hypercalcemic patients.

Impact of GABAA receptor gene variants (rs2279020 and rs211037) on the risk of predisposition to epilepsy: a case-control study.

Epilepsy is one of the most common neurological disorders with the incidence rate higher in developing states. It is a multifactorial ailment in which genetic diversity along with other factors plays an important role. The objective of this study was to assess the involvement of different risk factors including single nucleotide polymorphisms (SNPs) present in GABRA1 (rs2279020) and GABRG2 (rs211037) genes with the susceptibility to epilepsy in the targeted population. Blood samples of 180 subjects were taken and genotyped through tetra-primer amplification refractory mutation system-polymerase chain reaction technique. The obtained demographic and genotypic data were analyzed through different statistical tools including χ2 (chi-square) test and odds ratio. Parental consanguinity and family history of seizures were observed in a considerable number of cases of this study along with residency in industrial areas. But, no association of rs2279020 (χ2 = 0.900, P = 0.638) and rs211037 (χ2 = 0.045, P = 0.832) was observed with predisposition to epilepsy. However, GG genotype of rs2279020 was observed more in female cases as compared to male cases. Furthermore, TG haplotype was observed to be associated with the increased risk of developing epilepsy (χ2 = 9.097; OR = 2.586; P = 0.002). Genetic models also showed no correlation of the targeted SNPs with the susceptibility to epilepsy. The outcomes of the present study suggested that neither rs211037 nor rs2279020 were associated with increased susceptibility to epilepsy in the targeted population.

Maternal Vitamin D receptor gene variant genotype and its influence on preterm birth, low birth weight, and fetal death. A case-control study from Northeast India

With the background of association and importance of the Vitamin D receptor (VDR) pathway in pregnancy, we aimed to evaluate the significance of maternal VDR gene polymorphism in the pathophysiology of preterm pregnancy and associated complications. A total of 120 Preterm delivery (PTD) cases and 111 healthy term delivery(TD) cases were evaluated using PCR-RFLP based approach. The distribution of variant genotype for Apa I (AA + aA) and FokI (FF + fF) was significantly higher in TD cases (p < 0.001 and p = 0.003) compared to PTD cases whereas the genotype for TaqI (TT + tT) was comparable between TD and PTD cases (p = 0.368). The variant genotype ApaI (AA + aA) and TaqI (Tt + TT) was found to decreased the risk of PTD. No association with low birth weight (LBW) and fetal death for different haplotypes was observed. However, the individual homozygous genotype AA for ApaI was associated with the LBW (p = 0.001), and the TT genotype for TaqI was found to be associated with the increased risk of preterm birth (OR = 7.5, p = 0.004) as well as negative pregnancy outcome (p = 0.005). The study provides crucial information regarding the association of a particular VDR genotype with preterm birth and associated complications and it might hold a prognostic significance in the future.

The (Lack of) DNA Double-Strand Break Repair Pathway Choice During V(D)J Recombination.

DNA double-strand breaks (DSBs) are highly toxic lesions that can be mended via several DNA repair pathways. Multiple factors can influence the choice and the restrictiveness of repair towards a given pathway in order to warrant the maintenance of genome integrity. During V(D)J recombination, RAG-induced DSBs are (almost) exclusively repaired by the non-homologous end-joining (NHEJ) pathway for the benefit of antigen receptor gene diversity. Here, we review the various parameters that constrain repair of RAG-generated DSBs to NHEJ, including the peculiarity of DNA DSB ends generated by the RAG nuclease, the establishment and maintenance of a post-cleavage synaptic complex, and the protection of DNA ends against resection and (micro)homology-directed repair. In this physiological context, we highlight that certain DSBs have limited DNA repair pathway choice options.

Long-Term Weight Outcome After Bariatric Surgery in Patients with Melanocortin-4 Receptor Gene Variants: a Case–Control Study of 105 Patients

Pathogenic heterozygous MC4R variants are associated with hyperphagia and variable degrees of obesity. Several research groups have reported short-term weight loss outcomes after bariatric surgery in a few patients with MC4R variants, but lack of longer-term data prevents evidence-based clinical decision-making. Bariatric surgery patients with heterozygous (likely) pathogenic MC4R variants, from three collaborating centers in the Netherlands, France, and the UK, were compared to matched controls (matched 2:1 for age, sex, preoperative BMI, surgical procedure, and diabetes mellitus, but without MC4R mutations). Weight loss and regain outcomes up to 6years of follow-up were compared. At 60months of follow-up after RYGB, cases with MC4R variants showed weight regain with a mean of 12.8% (± 10.4 SD) total weight loss (TWL) from nadir, compared to 7.9% (± 10.5 SD) in the controls (p = 0.062). Among patients receiving SG, the cases with MC4R variants experienced inferior weight loss (22.6% TWL) during the first year of follow-up compared to the controls (29.9% TWL) (p = 0.010). This multicenter study reveals inferior mid-term weight outcomes of cases with MC4R variants after SG, compared to RYGB. Since adequate weight loss outcomes were observed after RYGB, this procedure would appear to be an appropriate surgical approach for this group. However, the pattern of weight regain seen in cases with MC4R variants after both RYGB and SG highlights the need for pro-active lifelong management to prevent relapse, as well as careful expectation management.

Association of MC1R variation and plumage color diversity of Nigerian domestic pigeon (Columba livia domestica)

Domestic pigeons (Columba livia domestica) have diverse plumage pigmentations. Melanocortin 1 receptor (MC1R) gene variation has been correlated with color traits. The association between MC1R and plumage coloration in African domestic pigeons is yet to be investigated. Herein, we report the relationships between single nucleotide polymorphisms (SNPs) in MC1R and plumage of 35 domestic pigeons from Nigeria with 4 different plumage phenotypes plus 37 published MC1R sequences from France (n = 14) and Russia (n = 11). We obtained 14 SNP sites among 72 individuals. Missense mutations C206T (Ser69Leu) and G253A (Val85Met) were observed in 16 and 8 Nigerian pigeons, respectively. The chi-squared test (p < 0.05) for C206T, G253A, and A520G has the advantage of homozygous genotypes CC, GG, and AA, respectively. The association of C206T loci showed the advantage of CC genotype in ash-red, spread, and white pigeons, and TT in blue-bar, spread, and white feather pigeons. For G253A and A520G loci, GG and AA were dominant in all plumages except for genotype AA in G253A, which was prominent in ash-red, spread, and white plumages. The three SNPs were assigned to seven haplotypes. The median-joining network revealed 20 haplotypes, including 5 in Nigeria and 2 shared. This study provides an insight into the association of MC1R variation and plumage diversity in Nigerian domestic pigeons. However, due to the limitation of the current data, we could not make further conclusions; this necessitates the need for more genomics studies on Nigerian pigeons.

A Case Report of Calcium- Sensing Receptor Gene Variant CASR (c.659G&gt;A; p.R220Q) and Primary Hyperparathyroidism

Background: Primary hyperparathyroidism (PHPT) results from excessive parathyroid hormone from one or more overactive parathyroid gland(s). An estimated 90% of PHPT cases are sporadic, and up to 10% are inherited, comprising hereditary hyperparathyroidism (HHPT). Genetic testing can aid in diagnosis and management and influence testing of other family members.