Significant Allelic Differences Research Articles

Application of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCRRFLP) Technique in the Analysis of MYO1H Single Nucleotide Polymorphism in Malay Mandibular Prognathism Patients

Genetic studies have reported the association between polymorphism in MYO1H with mandibular prognathism. MYO1H is found in skeletal muscle sarcomeres and is expressed in the mandibular jaw cartilage signifying its importance during craniofacial development. This study aimed to characterise the genotype and allele of MYO1H single nucleotide polymorphism (SNP) (rs3825393) and to associate the SNP with mandibular prognathism in Class III skeletal malocclusion. This was a case-control study, which involved 57 Malay subjects with 30 Class I (control) and 27 Class III skeletal base patients (case). Cephalometric measurements were taken prior to collection of saliva samples. MYO1H SNP (rs3825383) was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Chi-square (χ2) test was used to compare genotype and allele frequencies between the groups while Hardy-Weinberg Equilibrium (HWE) was applied to assess distribution of genotype frequency in both classes. MYO1H SNP (rs3825393) did not yield significant association with mandibular prognathism with p = 0.33; OR = 0.66; 95% CI = 0.289~1.518, that was reflected by no significant difference in allele (p > 0.05) and genotype (p > 0.05) frequency between control and study group. Nevertheless, AA genotype depicted the highest frequency in both groups. The genotype distribution in both groups was in concordance with HWE (p > 0.05). Our data showed no association of MYO1H SNP (rs3825393) with mandibular prognathism. Interestingly, we observed Allele A representing the major allele in Malay population. Presence of MYO1H SNP (rs3825393) was detected in samples analysed. Larger number of samples is required to confirm the involvement of MYO1H polymorphisms in mandibular prognathism.

Genetic variants of TCF7L2 gene and its coherence with metabolic parameters in Lithuanian (Kaunas district) women population with previously diagnosed gestational diabetes mellitus compared to general population

ObjectiveTo determine the association of genetic variants rs7901695, rs7903146, rs7895340, rs11196205, rs12255372 of transcription factor 7 like 2 (TCF7L2) gene and its coherence with metabolic parameters in Lithuanian (Kaunas district) women population with previously diagnosed gestational diabetes mellitus (GDM) and to compare the prevalence of TCF7L2 single nucleotide polymorphism (SNP) results to general population. MethodsWomen with previously diagnosed GDM participated in the study. Anthropometric measurements were taken. Carbohydrate and fat metabolism were evaluated. TCF7L2 SNP common variants (rs7901695, rs7903146, rs7895340, rs11196205, rs12255372) were set.The prevalence of TCF7L2 the same SNP alleles were also evaluated for women of the general population. The results were compared to the main study group (women with previously diagnosed GDM). The results were calculated in a ratio of 1:2. General population group comprised 300 women who were selected from the random sample of the Kaunas city population.Statistical analysis was made with the statistical package IBM SPSS Statistics version 21. Quantitative parametric variables presented as mean and standard deviation, qualitative variables – as absolute numbers and percentage. ANOVA test was used, for the comparison between three or more groups. Quantitative variables were compared using Student’s t-test. Categorical variables were compared using chi-square test. Correlation analysis of parametrical data was performed by Pearson’s correlation. Odds ratios (OR) with 95% CIs were presented. The results were considered statistically significant at p < 0.05. Results158 women with previously (15–47 years ago) diagnosed GDM participated in the study. The mean age of participants was 53.0 ± 8.2 years and 60.2 ± 7.5 years (p < 0.001), BMI – 31.4 ± 7.9 kg/m2 and 29.9 ± 5.8 kg/m2 (p < 0.001) in GDM group and general population respectively. GDM group women had significantly larger waist, hip circumference and waist to hip ratio compared to general population women: 98.9 ± 18.1 cm vs. 89.2 ± 13.3 (p < 0.001), 112.5 ± 14.8 cm vs. 105.6 ± 10.9 cm (p < 0.001), 0.87 ± 0.08 vs. 0.84 ± 0.07 (p < 0.001). There was no significant difference in blood pressure results between groups (p > 0.05).Carbohydrate dysmetabolism was set for 57.6% women with previously diagnosed GDM: 11 (7.0%) were diagnosed with impaired fasting glycemia (IFG), 14 (8.9%) with impaired glucose tolerance (IGT), type 2 Diabetes Mellitus (DM) was diagnosed for 58 (36.7%), DM type 1 for 7 (4.4%), MODY2 (maturity onset diabetes of the young) – 1 (0.6%) patients. TCF7L2 SNPs in women with previously diagnosed GDM and various carbohydrate metabolism groups did not differed (p > 0.05).Body weight, body mass index (BMI), waist and hip circumference in GDM group participants with different TCF7L2 SNP alleles did not differ (p > 0.05). There was no statistically significant difference in fasting plasma glucose (FPG), oral glucose tolerance test (OGTT) results, cholesterol levels and different TCF7L2 SNP alleles in GDM group (p > 0.05).We found higher prevalence of TCF7L2 SNP rs7901695 CC/CT, rs7903146 CT/TT and rs12255372 GT/TT alleles in women previously diagnosed GDM compared to general population women‘s group. The OR of being in GDM group with TCF7L2 SNP: rs7901695 CC/CT alleles, was 1.703 (95% CI 1.153–2.515); rs7903146 CT/TT – 1.708 (95% CI 1.149–2.538); rs12255372 GT/TT – 1.575 (95% CI 1.058–2.343). ConclusionsNo statistically significant difference in glucose, cholesterol levels and different TCF7L2 SNP alleles in GDM group was found. TCF7L2 SNPs did not differed in women with previously diagnosed GDM and various carbohydrate metabolism groups, though a significantly higher incidence of TCF7L2 rs7901695 SNP CC/CT, rs7903146 SNP CT/TT, rs12255372 GT/TT alleles in study subjects compared to the general population women were observed.

Beyond hybridization: the genetic impacts of nonreproductive ecological interactions of salmon aquaculture on wild populations

Cultured Atlantic salmon Salmo salar are of international socioeconomic value, and the process of domestication has resulted in significant behavioural, morphological, and allelic differences from wild populations. Substantial evidence indicates that direct genetic interactions or interbreeding between wild and escaped farmed Atlantic salmon occurs, genetically altering wild salmon and reducing population viability. However, genetic interactions may also occur through ecological mechanisms (e.g. disease, parasites, predation, competition), both in conjunction with and in the absence of interbreeding. Here we examine existing evidence for ecological and non-reproductive genetic interactions between domestic Atlantic salmon and wild populations and the potential use of genetic and genomic tools to resolve these impacts. Our review identified examples of genetic changes resulting from ecological processes, predominately through pathogen or parasite transmission. In addition, many examples were identified where aquaculture activities have either altered the selective landscape experienced by wild populations or resulted in reductions in population abundance, both of which are consistent with the widespread occurrence of indirect genetic changes. We further identify opportunities for genetic or genomic methods to quantify these impacts, though careful experimental design and pre-impact comparisons are often needed to accurately attribute genetic change to aquaculture activities. Our review indicates that ecological and non-reproductive genetic interactions are important, and further study is urgently needed to support an integrated understanding of aquaculture-ecosystem interactions, their implications for ecosystem stability, and the development of potential mitigation and management strategies.

Association of Leptin Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Population

Background Recently, increasing studies have revealed that leptin is involved in the development of rheumatoid arthritis (RA). This study is aimed at exploring the association of leptin gene single nucleotide polymorphisms (SNPs) with susceptibility to RA in a Chinese population. Methods We recruited 600 RA patients and 600 healthy controls from a Chinese population and analyzed their three leptin SNPs (rs10244329, rs2071045, and rs2167270) using the improved Multiplex Ligase Detection Reaction (iMLDR) assays. The associations of these SNPs with clinical manifestations of RA were also analyzed. Enzyme-linked immunosorbent assay (ELISA) was performed for plasma leptin determination. Results No significant difference in either allele or genotype frequencies of these three SNPs between RA patients and healthy controls was observed (all P > 0.05). Association between the genotype effects of dominant, recessive models was also not found (all P > 0.05). No significant difference in plasma leptin levels was detected between RA patients and controls (P > 0.05). Conclusion Leptin gene (rs10244329, rs2071045, and rs2167270) polymorphisms are not associated with RA genetic susceptibility and its clinical features in the Chinese population.

Positive association between PTN polymorphisms and schizophrenia in Northeast Chinese Han population.

As a severely and highly heritable psychotic disorder, schizophrenia has become a serious public health problem in modern society. Pleiotrophin (PTN) is a secreted cell cytokine associated with the extracellular matrix and acts as a growth factor. PTN is mainly expressed in neuroectodermal and mesodermal tissues, indicating its effect in neuron migration and epithelium-mesenchyme interactions. Whereas PTN is associated with some neurodegenerative diseases and has modulating effects on them. In this study, we aimed to investigate the association between PTN polymorphisms and schizophrenia in an independent case-control sample-set including 738 schizophrenia patients and 1085 healthy controls. Of the 13 selected single nucleotide polymorphisms (SNPs), five showed significant differences in allele or/and genotype frequencies between patients and controls: rs3959914 (genotype: χ = 11.5217, P = 0.0032); rs11765480 (genotype: χ = 10.6620, P = 0.0049); rs1473355 (genotype: χ = 8.3902, P = 0.0151); rs322246 (allele: χ = 5.5954, P = 0.0180); rs322240 (genotype: χ = 8.8429, P = 0.0121; allele: χ = 8.7802, P = 0.0031). The haplotype analysis of the selected SNPs showed different haplotype frequencies for one block (rs322240, rs322246) between cases and controls (global: χ = 9.0290, P = 0.0110; A-G: χ = 8.985, P = 0.0027; C-A: χ = 5.814, P = 0.0159). Our present results indicate PTN as a susceptibility gene for schizophrenia.

SNP rs1803622 in hsa-miR-548g binding site at GAPDH alters susceptibility to breast cancer

Breast cancer has been increasing in developing countries; this cancer is becoming a fundamental health problem for these countries. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a classical glycolytic enzyme correlated with the hormonal receptor concentrations, cell proliferation, tumor grade and stage, drug resistance, and outcome of breast cancer cells. Furthermore, genetic variations in miRNA binding sites could be played an essential role in breast cancer risk and survival. In this study, the SNP rs1803622 at the 3′-UTR of GAPDH was chosen as a candidate SNP for investigation based on bioinformatics studies. This polymorphism was genotyped in an Iranian population with 123 breast cancer patients and 117 matched healthy controls using the Allele-Specific Primer (ASP)-PCR method. The functional impact of this genetic variation on the post-transcriptional regulation of GAPDH gene were bioinformatically studied. The genotyping data, for the first time, successfully identified frequencies of GG, GT, and TT to be 7%, 61%, and 32% in breast cancer patients, respectively. In particular, the assessed frequencies of allele G was 38% while risk allele T was 62% in these population. Results revealed that compared with the GG genotype of rs1803622, T allele was related to a significantly increased risk of breast cancer in a dominant genetic model Significant difference in allele and genotype distributions in the SNP rs1803622 was found between the high and low expression levels of estrogen, progesterone, and HER2 receptors. Furthermore, allele and genotype frequencies in the SNP rs1803622 were also related to the stage and grade of breast cancer. Surprisingly, Genotype and allele frequencies in this SNP were also significantly different in metastatic and non-metastatic breast cancer samples. Finally, the bioinformatics data suggested that the SNP rs1803622 might be involved in transcriptional regulation of the GAPDH gene by hsa-miR-548g.

The association between serotonin-related gene polymorphisms and susceptibility and early sertraline response in patients with panic disorder

BackgroundA number of studies have shown that genetic factor plays an important role in etiology of panic disorder (PD). The aim of the present study was to examine the association of serotonin-related gene polymorphisms with PD risk. Then, we analyzed the correlation between these gene polymorphisms and response to sertraline drug.MethodsTwo hundred thirty-three patients with PD and 231 healthy controls were enrolled in the study. Panic Disorder Severity Scale (PDSS) were administered to all subjects, and all patients in the study were also assessed after 4 weeks of treatment. The SLC6A4(rs140701, rs3813034, 5-HTTLPR and STin2), 5-HTR1A rs6295, 5-HTR2A rs6313 and COMT rs4680 gene polymorphisms were genotyped and assessed for the potential association.ResultsThe allelic model showed that the SLC6A4 rs140701 polymorphism variant was significantly associated with increased risk of PD (OR = 0.624, 95% CI 0.450–0.864, p < 0.05), and a significant result was found in the dominant model (OR = 0.546; 95% CI, 0.371–0.804, p < 0.05). There was a significant difference in allele and genotype frequency between responders and nonresponders in the 5-HTTLPR polymorphism (OR = 0.205, 95% CI 0.128–0.328; OR = 0.249, 95% CI 0.155–0.401, both p < 0.001), indicating the PD patients with S-allele had a poorer response to sertraline than L-allele carriers.ConclusionsThe present study suggests that the SLC6A4 rs140701 polymorphism variant may be associated with susceptibility to PD, and 5-HTTLPR polymorphism may be a predictor of response to sertraline in the treatment of PD.

Determining the association between polymorphisms of the DAT1 and DRD4 genes with attention deficit hyperactivity disorder in children from Java Island.

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurobehavioural in the children. Genetic factor is known one of the factors which contributed in ADHD development. VNTR polymorphism in 3’UTR exon 15 of DAT1 gene and exon 3 of DRD4 gene are reported to be associated in ADHD. In this study we examine the association of ADHD with VNTR polymorphism of DAT1 and DRD4 gene in Indonesian children. Sixty-five ADHD children and 70 normal children (6-13 years of age), were included in the study, we matched by age and gender. ADHD was diagnosed by DSM-IV. We performed a casecontrol study to found the association between ADHD and VNTR polymorphism of DAT1 and DRD4 genes. The 10-repeat allele of DAT1 and 2-repeat allele of DRD4 were higher in Indonesian children. Although the frequency of these allele was higher, but it was similar both in ADHD and control groups. Neither DAT1 nor DRD4 gene showed showed significant difference in genotype distribution and frequency allele between both groups (p > 0.05). No association between ADHD and VNTR polymorphism of DAT1 and DRD4 genes found in Indonesian children. This data suggest that DAT1 and DRD4 do not contribute to etiology of ADHD in Indonesian children. Further studies are needed to clarify association between VNTR polymorphism of DAT1 and DRD4 genetic with ADHD of Indonesian children in larger sample size and family based study.

Association Analysis of ANRIL Polymorphisms and Haplotypes with Autism Spectrum Disorders.

Autism spectrum disorder (ASD) has been shown to have a complex inheritance. Several single-nucleotide polymorphisms (SNPs) have been shown to be associated with risk of this neurodevelopmental disorder. In the current study, we genotyped four SNPs in a genomic hotspot for human disorders. The selected SNPs were located in adjacency of the antisense noncoding RNA in the INK4 locus (ANRIL) and have been shown to be associated with a number of human disorders. Genotyping was performed in 420 ASD cases and 420 normally developed children. After correction of P values for multiple comparisons, there was no significant difference in frequencies of rs1333045, rs1333048, rs4977574, and rs10757278 alleles, genotypes, or haplotypes between ASD children and children with normal development. However, one estimated haplotype (T A A A haplotype corresponding to rs1333045, rs1333048, rs4977574, and rs10757278 SNPs, respectively) tended to be more prevalent among cases compared with controls (OR (95% CI) = 1.77 (1.19-2.64), adjusted P value = 0.07). Besides, the T A G G tended to be less common among ASD cases compared with controls (OR (95% CI) = 0.64 (0.47-0.87), adjusted P value = 0.07). Although we could not detect significant difference in alleles, genotypes, or haplotypes frequencies between cases and controls, the trend toward association between two haplotypes and ASD risk implies that there might be a putative causative variant in the mentioned haplotypes whose association with ASD could be determined in larger cohorts of patients.

Lack of associations between lactoferrin (LTF) and mannose-binding lectin 2 (MBL2) gene polymorphism and dental caries susceptibility.

ObjectiveWith the development of human genomics, the genetic factors associated with dental caries have receiving increasing attention. This study was performed to evaluate the relationship between lactoferrin (LTF) and mannose-binding lectin 2 (MBL2) gene single nucleotide polymorphisms (SNPs) and dental caries susceptibility in Chinese children.MethodsThis prospective case–control study included 360 unrelated children (aged 12–15 years) who received oral health examinations and questionnaire surveys. The children were divided into two groups by counting the numbers of decayed, missing, and filled teeth (DMFT/dmft): case group (n = 162, DMFT/dmft ≥ 1) and control group (n = 198, DMFT/dmft = 0); non-invasive saliva samples were collected to extract genomic DNA. Six SNPs (rs2073495C/G, rs1042073C/T, rs10865941C/T, and rs1126477A/G in LTF; rs7096206C/G and rs7095891G/A in MBL2) were tested by mass spectrometry.ResultsThe study included 360 individuals with (85 boys and 77 girls) and without a history of caries (96 boys and 102 girls). There were no statistically significant differences in alleles and genotypes among the six SNPs between the two groups.ConclusionThere is no evidence that polymorphisms of LTF and MBL2 genes are associated with dental caries susceptibility in populations from northwest China; further confirmation is needed with larger sample sizes.

Single Nucleotide Polymorphisms of FCRL3 in Iranian Patients with Behcet’s Disease

Both genetic and environmental factors influence, susceptibility to autoimmune disorders including Behcet's disease (BD). FCRL3 (Fc receptor like 3 genes), a novel immunoregulatory gene, has recently been reported as a new promising candidate gene for general autoimmunity. This study was conducted to explore the potential association of FCRL3 polymorphisms with BD. This study was conducted from 2010 to 2015 in Tehran University of Medical Sciences, Tehran, Iran. Four single-nucleotide polymorphisms of FCRL3 (rs7528684, rs11264799, rs945635, and rs3761959) were genotyped in 220 patients and 220 healthy controls. Typing of the polymorphisms in this case-control study was carried out using polymerase chain reaction-restriction fragment length polymorphism analysis. Analysis of the alleles revealed a significantly lower frequency of the A allele at the -169 site (rs7528684) in BD patients compared with that in controls (P=0.000, 66.4% versus 82%, χ2= 30.23). Moreover, a significant lower frequency of AA genotype and higher frequency of GG genotype was recorded for rs7528684. There was also relationship between posterior uveitis as a clinical sign of disease and polymorphism of allele A at the -169 site (P=0.015). This study revealed a significant difference in both allele and genotype frequency at position -169 of FCRL3 gene between Iranian patients with BD and normal subjects. These data suggest FCRL3 gene polymorphisms might be the autoimmunity risk factor for BD.

Identification of the novel polymorphisms and potential genetic features of the prion protein gene (PRNP) in horses, a prion disease-resistant animal

Prion diseases, a protein misfolded disorder (PMD) caused by misfolded prion protein (PrPSc), present in a wide variety of hosts, ranging from ungulates to humans. To date, prion infections have not been reported in horses, which are well-known as prion disease-resistant animals. Several studies have attempted to identify distinctive features in the prion protein of horses compared to prion disease-susceptible animals, without the study on polymorphisms of the horse prion protein gene (PRNP). Since single nucleotide polymorphisms (SNPs) of PRNP in prion disease-susceptible animals are major susceptibility factors, the investigation of SNPs in the horse PRNP gene is important; however, only one study investigated a single horse breed, Thoroughbred. Thus, we investigated genetic polymorphisms and potential characteristics of the PRNP gene in 2 additional horse breeds. To this end, we performed amplicon sequencing of the horse PRNP gene and investigated SNPs in Jeju and Halla horses. We compared genotype, allele and haplotype frequencies among three horse breeds, namely, Thoroughbred, Jeju and Halla horses. In addition, we evaluated the potential influence of the identified nonsynonymous SNPs on the prion protein using PolyPhen-2, PROVEAN, and PANTHER. Furthermore, we measured the aggregation propensity of prion proteins using AMYCO and analyzed linkage disequilibrium (LD) between PRNP and prion-like protein gene (PRND) SNPs. A total of 4 SNPs were found, including two nonsynonymous SNPs (c.301 T > A, c.525 C > A) and three novel SNPs (c.-3A > G, c.301 T > A and c.570 G > A). There were significant differences in genotype, allele and haplotype frequencies among the three horse breeds. The nonsynonymous SNP, c.301 T > A (W101R), was predicted to be benign, deleterious, and possibly damaging by PolyPhen-2, PROVEAN and PANTHER, respectively. In addition, the amyloid propensity of horse prion protein according to 4 haplotypes of nonsynonymous SNPs was predicted to be benign by AMYCO. Finally, we identified weak LD between PRNP and PRND SNPs.

NAD(P)H: quinone oxidoreductase 1 gene rs1800566 polymorphism increases the risk of cervical cancer in a Chinese Han sample: A STROBE-complaint case-control study.

Recently, 2 studies from Thai and American investigated the relationship between NAD(P)H: quinone oxidoreductase 1(NQO1) gene rs1800566 polymorphism and cervical cancer risk and generated contrary results. However, no Chinese reports have addressed this relationship until now. To explore the association between NQO1 gene rs1800566 polymorphism with cervical cancer, we performed a study in a Chinese Han sample.Using a unmatched case-control design, we enrolled 450 cervical cancer patients and 568 controls in the Central Hospital of Wuhan from January 2010 to December 2016. The genotypes were determined by sequencing polymerase chain reaction product. Hardy-Weinberg equilibrium was assessed using the Chi-square test. The univariate and multi-variate logistic regression with odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the association between the NQO1 gene rs1800566 polymorphism and cervical cancer susceptibility.The Chi-square test indicated that significant allele and genotype distributions differences were observed between case group and control group (P < .001). The logistic regression indicated that TT genotype was associated with higher risk of cervical cancer compare with those with the CT or CC genotype (TT vs CC: OR = 2.82, 95%CI: 1.91–4.17, P < .001; TT vs CT: OR = 2.02, 95%CI: 1.36–3.01, P < .001). The effects of NQO1 show dominant model (TT/CT vs CC: OR = 1.67, 95%CI: 1.30–2.15, P < .001) and recessive model (TT vs. CT/CC: OR = 2.43, 95%CI: 1.68–3.52, P < .001). The significant relationship between NQO1 rs1800566 polymorphism and cervical cancer risk was also found in stratified analyses. The cross-over analysis indicated that there are potential interactions between genetic factors and human papillomavirus infection/ contraceptive oral use for the risk of cervical cancer.NQO1 gene rs1800566 polymorphism is associated with elevated risk of cervical cancer in Chinese Han women. The interactions between rs1800566 polymorphism and human papillomavirus infection/ contraceptive oral use further reinforce this association.

High Frequency of the Opioid Receptor µ-1 (OPRM1) A118G Polymorphism, an Opioid Drug Therapy Related Gene, in the Indonesian Population

Background: The opioid receptor μ-1 (OPRM1) has become one of the most studied genes in pharmacogenetics, as this gene encodes the μ-opioid receptor (MOR), which plays a role in opioid drugs response, as well as in various disorders. One of its variants, A118G, which is found at a high frequency in the Asian population, has been associated with loss of sensitivity to and an increased requirement for analgesics in the treatment of pain, increased pain sensitivity, various types of substance dependencies, and the development of breast cancer. However, there are still limited reports about this gene polymorphism in the Indonesian population. Objective: The study aimed to determine the allele frequencies of the OPRM1 A118G polymorphism among the Indonesian population. Method: A cross-sectional study of 158 subjects, comprising 79 males and 79 females, was conducted among Indonesians, and genotype analysis was carried out by a modified allele-specific Polymerase Chain Reaction (PCR) method. Results: A frequency of 60.4% was found for the G allele among Indonesian samples, with a higher frequency being present in males (66.5%). The A allele was found at frequencies of 33.5% and 45.6% in males and females, respectively. A significant difference in allele frequency was found between males and females (p = 0.029, OR = 1.659, 95% CI [1.052–2.614]), while there was no significant difference in genotype frequencies between groups. Conclusion: A high prevalence of the OPRM1 A118G polymorphism was found in the Indonesian population, with the G allele frequency tending to be higher in males.

The relationship between elevated serum uric acid and arterial stiffness in a healthy population.

This study aims to investigate the relationship between serum uric acid and arterial stiffness in a healthy population. Among the 979 participants, baPWV was non-invasively measured, the circulating levels of uric acid were tested, and the uric acid polymorphisms (rs2231142 and rs11722228) were genotyped. Then, the Mendelian randomization method was employed to test the relationship between serum uric acid and arterial stiffness in a healthy population. After adjusting for age, gender, antihypertensive medication, body mass index, waist-to-hip ratio, urea nitrogen, creatinine and diabetic mellitus, there was a significant allelic difference in uric acid levels for each genotype (P < 0.0001 for rs2231142; P = 0.007 for rs11722228). However, there were no differences on the potential confounders between the genotypes of rs2231142 and rs11722228 (P > 0.05). The baPWV was significantly associated with circulating levels of uric acid after adjusting for cardiovascular risk factors and other potential confounders (P = 0.002). However, neither the single polymorphism, nor the accumulation of culprit alleles was associated with baPWV (P = 0.92 for rs2231142; P = 0.60 for rs11722228; P for trend = 0.77 for the combined analysis of culprit alleles). These results do not support the causal role of circulating levels of uric acid in the development of arterial stiffness.

Variation analysis of Ghrelin gene in Chinese patients with obesity, having polycystic ovarian syndrome

Association of single-nucleotide polymorphisms (SNPs) of the ghrelin gene with polycystic ovary syndrome (PCOS)is unclear. However, their correlation with PCOS-related obesity has been observed. The objective of this study was to evaluate the effects of ghrelin gene SNPs on PCOS-related obesity in Chinese women. The full-length sequence of the ghrelin gene was determined to explore the relationship of the SNPs with PCOS-related obesity in Chinese women. The gene was sequenced, including all exons, introns and exon–intron boundaries in 230 Han Chinese women with PCOS and 162 normal women. Significant genotypic and allelic differences were observed between the obese PCOS group and obese control group at rs35681 locus (p = .013 and .017). The genotypic analysis of obese and non-obese people in the PCOS group showed that the proportion of A allele in the obese PCOS group (10.9%) was higher than that of the G allele (3.6%). This study revealed that ghrelin rs35681 might be related to the occurrence of obesity associated with PCOS, and allele A was found to increase the risk of obesity in PCOS.

ASSESSMENT OF ESTROGEN RECEPTOR GENE POLYMORPHISM (T-397C VARIANT) IN PATIENTS WITH PREMENSTRUAL SYNDROME

The aim:of the study is to determine the frequency of polymorphism of estrogen receptor gene ESR1 (T-397C variant) in patients with premenstrual syndrome. Materials and methods: 50 women with diagnosis of premenstrual syndrome (the basic group) and 25 persons without it (the control group) were examined. Polymerase chain reaction was used to study T-397C polymorphism of estrogen receptor gene ESR1. Results:There was no significant difference in allele and genotype rates of ESR1 gene between persons with premenstrual syndrome and controls. TT genotype was determined in 24.0 % women in the control group and 24 % of patients in basic group (OR=1.00, 95 % CI=0.32-3.08, p=1.00), TC genotype - in 52.0 % and 46.0 % of individuals respectively (OR=0.79, 95 % CI=0.30-2.06, p=0.62), CC genotype - 24.0 % and 30.0 % of women respectively (OR=1.36, 95 % CI=0.45-4.07, p=0.59). Also, the frequency of T allele and C allele was similar in individuals with pathology and healthy women. There was no significant difference in allele and genotype rates of T-397C variant of ESR1 gene between patients with mild and severe forms of premenstrual syndrome and controls. Conclusions: There is no association of T-397C polymorphic variant of estrogen receptor gene ESR1 with the development of premenstrual syndrome.

Genetic variations associated with spleen-yang deficiency pattern of non-alcoholic fatty liver disease: A candidate gene study

IntroductionIn traditional Chinese medicine (TCM) clinical practice, Spleen-Yang deficiency pattern (SYDP) is the basic and core pattern present in non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the role of the susceptibile gene polymorphisms for NAFLD in SYDP in a Chinese Han population. MethodsA total of 12 single nucleotide polymorphisms (SNPs) were genotyped in 341 healthy subjects for control group and 341 subjects for NAFLD group (including 163 subjects for SYDP group and 178 subjects for non-SYDP group). Hardy-Weinberg equilibrium, allele and genotype frequency distribution, genotype association analysis, linkage disequilibrium (LD) and haplotype analysis were calculated. ResultsBetween the SYDP group and the control group: rs1260326, rs780094 and rs780093 in glucokinase regulator (GCKR) demonstrated significant differences in allele and genotype frequency distribution. Genotype association analysis showed the three SNPs all increased SYDP risk after adjustment for confounding factors. There was no significant deviation of the three SNPs between the non-SYDP group and the control group. The three SNPs were identified as a strong LD block and the haplotype TTT increased SYDP risk. In SYDP group, the allele C of the three SNPs showed a decreasing trend with an increase in the degree of SYDP. Additionally, the SYDP subjects with the mutant type CT/TT of rs1260326 and rs780094 had higher SYDP scores. ConclusionsThe rs1260326, rs780094 and rs780093 in GCKR were significantly associated with SYDP in NAFLD, as well as the degree of SYDP. GCKR polymorphisms might be a potential genetic biomarker of SYDP, as well as NAFLD.

Association of Neuregulin 1 rs7835688 G > C, rs16879552 T > C and rs2439302 G > C Polymorphisms with Susceptibility to Non-Syndromic Hirschsprung’s Disease

Background Hirschsprung’s disease (HSCR) is a heterogeneous congenital malformation of the enteric nervous system with a complex genetic etiology. We investigated if there was an association between Neuregulin-1 (NRG1) rs7835688 G > C, rs16879552 T > C and rs2439302 G > C polymorphisms and the risk of HSCR. Methods: We determined and compared the frequency of NRG1 polymorphisms rs7835688 G > C, rs16879552 T > C and rs2439302 G > C in 70 children with HSCR and 90 controls by TaqMan SNPs genotyping assays. Results: No significant differences in allele or genotype frequencies of NRG1 rs7835688 G > C, rs16879552 T > C and rs2439302 G > C polymorphisms were observed between HSCR cases and controls. Analyses showed that the NRG1 rs7835688 G > C, rs16879552 T > C and rs2439302 G > C polymorphisms were not significantly associated with an increased risk of non-syndromic HSCR. Conclusions: Our findings suggested that NRG1 rs7835688 G > C, rs16879552 T > C and rs2439302 G > C polymorphisms are not a risk factor in development of HSCR.

Genetically Elevated Serum Uric Acid and Renal Function in an Apparently Healthy Population

Background: The association between uric acid and kidney disease has been extensively investigated. Numerous studies have reported the association between circulating levels of uric acid and renal function. Objectives: To test, by the Mendelian randomization method, whether there is a causal association between circulating levels of uric acid and renal function. Methods: In 989 participants, estimated glomerular filtration rate (eGFR) was calculated, the circulating level of uric acid was tested, and the uric acid polymorphism (rs11722228) was genotyped. Results: After adjusting for age, gender, smoking history, alcohol intake, antihypertensive medication, body mass index, waist-to-hip ratio, and levels of urea nitrogen and creatinine, a significant allelic difference was found in uric acid levels for each genotype (p < 0.0001). Furthermore, the circulating levels of uric acid were negatively associated with eGFR after adjusting for cardiovascular risk factors and other potential confounders (p < 0.0001). Meanwhile, eGFR was significantly associated with the genotypes of rs11722228 (β = –0.07; p = 0.02). Conclusions: Evidence from the Mendelian randomization approach implied a causal relationship between uric acid and renal function in an apparently healthy population.