Significant Differences In Genotype Frequencies Research Articles

Molecular characterization of tyrosinase gene (exon 1) in camels of Saudi Arabia

We detected genetic variations and single nucleotide polymorphisms (SNPs) of tyrosinase gene (Tyr) among seven camel populations in Saudi Arabia. Exon 1 of TYR was amplified from 166 DNA samples representing six indigenous camel populations and one exotic population (Alsumalia) that yielded a 474-bp fragment. Two SNPs (T/C) were detected at coding positions 200 and 523 bp. Significant differences in genotypic frequencies were observed at coding position 200. Three different genotypes (CC, TT, CT) were detected at position 200 in each studied population, except Alsumalia, which only had CT. At position 523, the CC genotype was detected in Majaheem and TT was detected in the other populations. The C allele dominated over T allele suggesting that coat color might be associated with it. The populations Majaheem, Maghateer, Hamra, Sofr, and Sawahli had higher C allele frequency than Shaul and the exotic Alsumalia. The cluster analysis of genotypic frequencies at positions 200 and 523 indicated that Majaheem was not closely related to other Saudi populations. The detection of polymorphism at position 523 in Majaheem and in wild Bactrian camel led us to conclude that wild Bactrian camel could be the immediate ancestor of Majaheem populations and other Saudi Arabian populations, as well.

RANKL Gene Polymorphism as a Potential Biomarker to Identify Acute Charcot Foot Among Indian Population With Type 2 Diabetes: A Preliminary Report.

Studies addressing the link between gene polymorphism and Charcot neuropathic osteoarthopathy (CN) have been limited to analyse osteoprotegerin gene. Aim is to understand the association of RANKL gene variants on the susceptibility of diabetic neuropathy and CN and to measure the serum levels of sRANKL among Indian population with type 2 diabetes. 77 subjects (48 males: 29 females) were recruited and divided into 3 groups. Group 1 Control: normal glucose tolerance (NGT). Group 2: Type 2 diabetes mellitus and neuropathy (DPN). Group 3: Established type 2 diabetes mellitus, DPN, and CN. Subjects were genotyped for RANKL SNP 693 C/G and 643 C/T using polymerase chain reaction-restriction fragment length polymorphism. sRANKL levels were measured using ELISA (enzyme-linked immunosorbent assay). The serum levels of sRANKL were significantly different between the 3 groups. In RANKL -643 C/T the frequency of "CT" genotype and the minor allele "T" was greater among the DPN and CN group compared with the NGT. Further statistical analysis found a significant difference in genotypic frequencies between DPN and NGT subjects with CT genotype. In RANK L -693 C/G the frequency of homozygote mutant "GG" and the minor allele "G" was greater among the DPN and CN group compared with the NGT. Significant differences in genomic frequencies were observed among "GG" genotype. RANKL -643 C/T was significantly associated with DPN alone while -693 C/G was significantly associated with both DPN and CN. Thus, the study suggests RANKL polymorphism might be considered as an independent risk factor for the development of CN.

Abstract 1617: Genetic polymorphisms in DNA repair genes XRCC1 and 3 are associated with increased risk of breast cancer in Bangladeshi population

Abstract Background: Breast cancer is the most commonly occurring cancer in women worldwide and its prevalence vary among different ethnic groups. Genetic polymorphisms in DNA repair genes may affect individual variation in DNA repair capacity which may contribute to individual susceptibility for developing various cancers. This study aimed to investigate the contribution of polymorphisms in two DNA repair genes, namely XRCC1 (Arg399Gln, rs25487) and XRCC3 (Thr241Met, rs861539) to breast cancer risk in Bangladeshi females and their role as susceptibility markers. Methods: A case-control study comprising 121 breast cancer patients and 133 healthy volunteers was conducted taking the age, breast feeding status, menopausal status, education etc into account. Genomic DNA isolated from peripheral blood was used to genotype the target polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Risk-stratified subgroup analyses were conducted to find out the association between the genotypes and age-, menopause-, lactating status-related characteristics of breast cancer patients. Results: A significant positive association was found between XRCC1 (Arg399Gln,) and XRCC3 (Thr241Met) polymorphisms and breast cancer risk in the studied population. In case of XRCC1 Arg399Gln polymorphism, the heterozygous Arg/Gln (G/A) and homozygous Gln/Gln (A/A) genotypes showed 1.78-fold (OR=1.78, 1.0084 to 3.1442, p=0.0467) and 2.41-fold (OR=2.41, 95% CI= 1.0354 to 5.5914, p=0.0413) increased risk of breast cancer, respectively when compared with homozygous Arg/Arg genotype. The presence of any XRCC1 Gln (Arg/Gln or Gln/Gln) was associated with 1.93-fold increased risk (OR=1.93, 95% CI= 1.1574 to 3.2290, p=0.0118). The variant Gln (A) allele also was associated with increased risk of breast cancer (OR=1.78, 95% CI= 1.1885 to 2.6805, p=0.0052). The Gln/Gln genotype was more prevalent in breast cancer cases at ages 55 or above and in menopausal state. In case of XRCC3 (Thr241Met) polymorphism, Thr/Met (C/T) heterozygote, and combined Thr/Met+Met /Met (C/T+T/T) genotypes were significantly associated with 1.85- and 1.89- fold higher risk of breast cancer, respectively (OR=1.85, 95% CI=1.0815 to3.1834, p=0.0248; OR=1.89, 95% CI=1.1199 to 3.1908, p=0.0171, respectively). The variant Met (T) allele showed significant association with increased susceptibility (1.70-fold) to breast cancer (OR=1.70, 95% CI=1.0849 to 2.6172, p= 0.0206). Among breast cancer cases significant differences in genotype frequency were evident in patients with age 55 years or above and with menopause. Conclusion: Our results suggest that XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) polymorphisms are associated with increased risk of breast cancer in Bangladeshi females. In addition, this association was significantly related to age and lactating status. Citation Format: Md. Mustafizur Rahman, Nupur Rani Hawlader, Md. Mostafizur Rahman, Md. Amir Hossain. Genetic polymorphisms in DNA repair genes XRCC1 and 3 are associated with increased risk of breast cancer in Bangladeshi population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1617.

Correlation between polymorphisms of surfactant protein A1 rs1059047 and rs1136450 and respiratory distress syndrome in Mongolian premature infants

Objective To study the correlation between polymorphisms of surfactant protein A1 rs1059047 and rs1136450 and respiratory distress syndrome (RDS) in Mongolian premature infants in Inner Mongolia. Methods Totally 50 Mongolian RDS premature infants in our ward were recruited as the case group (33 males and 17 females), and another 50 Mongolian non-RDS premature infants with same ethnicity, same sex and gestational age were served as the control group (29 males and 21 females). Single nucleotide polymorphisms of SP-A1 rs1059047 and, rs1136450 and allele haploids (6A, 6A2, and 6A3) were detected by polymerase chain reaction-single strand conformation polymorphism gene detection technology and were compared between the case and control groups. Results Three genotypes, CC, TT, CT were detected in the case and control groups at rs1059047, all of which were mainly TT genotype. There was no significant difference in genotype frequency between the two groups (χ2=1.429, P > 0. 05). Two genotypes, CG and GG, were detected in the case and control groups at rs1136450, and CG was the dominant genotype. There was no significant difference in genotype frequency between the two groups (χ2= 1.624, P>0.05). The distribution frequency of SP-A1 allele haploids (6A, 6A2, 6A3) in the case group was 36%, 68% and 42%, respectively, and 62%, 46% and 50% in the control group, respectively. There was no significant difference in the frequency of allele haploid 6A3 between the two groups (χ2=0.502, P>0.05); but there was a significantly difference in the frequency of allele haploids (6A, 6A2) between the two groups (χ2=6.763, 4.937, P<0.05). Conclusions The alleles and allele frequency of SP-A1 (rs1059047, rs1136450) were not associated with RDS in Mongolian premature infants. However, SP-A1 allele haploid 6A2 is the susceptible gene for RDS in Mongolian premature infants, and haploid 6A is the protective gene. Key words: Surfactant protein-A1; Respiratory distress syndrome; Mongolian premature infants; Gene variants

MTHFR gene polymorphisms in hypothyroidism and hyperthyroidism among Jordanian females.

Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA methylation that is associated with autoimmune pathology. We investigated the association between MTHFR genetic polymorphisms at g.677C>T and g.1298A>C and their haplotypes, and the risk of thyroid dysfunction among Jordanian females. A case-control study involving 98 hypothyroidism cases, 66 hyperthyroidism cases and 100 controls was conducted. Polymerase chain reaction/restriction fragment length polymorphism technique was performed to determine genotypes. Statistical analysis using SPSS software was performed. Genetic analysis showed a significant difference in genotype frequency of g.1298A>C between cases, and controls [hypothyroidism: AA (45.9%), AC (37.8%), CC (16.3%); hyperthyroidism: AA (9.1%), AC (69.7%), CC (21.2%); controls: AA (37.8%), AC (29.6%), CC (32.7%); CChypo vs. AAhypo: 2.55, 95% CI: (1.18-5.52); OR at least on Chypo: 1.79, 95% CI: (1.07-2.99)]; CChyper vs. AAhyper: 4.01, 95% CI: (1.79-9.01); OR at least on Chyper: 0.18, 95% CI: (0.07-0.48)]. There was no significant difference in genotype frequency of g.677C>T between cases and controls [hypothyroidism: CC (50.0%), CT (32.7%), TT (17.3%); hyperthyroidism: CC (77.3%), CT (15.2%), TT (7.6%); controls: CC (55.6%), CT (32.3%), TT (12.1%)]. There was a significant difference of MTHFR haplotypes among hypothyroidism cases and controls. TA and CC had a lower hypothyroidism risk whereas; TC showed a higher risk. g.1298A>C genetic polymorphism of MTHFR may modulate the risk of thyroid disease. CC, TA, and TC haplotypes affect the risk of hypothyroidism. Larger samples should be included in the future to verify the role of MTHFR polymorphisms in thyroid diseases.

The association of Intron 4 VNTR and Glu298Asp polymorphisms of the nitric oxide synthetase 3 gene and vasculogenic erectile dysfunction in Turkish men

ABSTRACTSeveral studies have focused on the impaired role of endothelial nitric oxide synthase (NOS3) gene polymorphism and its association to erectile dysfunction (ED). However, currently controversial results have been reported due to their significant heterogeneity. The present study aimed to assess the genotypic distribution and the allelic frequency of Intron 4 VNTR and Glu298Asp gene polymorphisms in vasculogenic ED patients compared to healthy controls of a specific region of Turkey. A total of 75 patients with ED (median age: 56, IQR:10.5) and 75 healthy controls (median age: 56, IQR:10.5) were prospectively analyzed. All subjects were equally evaluated by the same physician with detailed history-taking, physical examination, International Index of Erectile Function (IIEF) questionnaire, and blood tests (incl. glucose, testosterone, triglyceride and total cholesterol level). Those with an IIEF score under 26 were considered to have ED, by classifying them according to their scores as mild (22–25), moderate (11–21) and severe (1–10) ED. Color doppler ultrasonography was carried out in patients with an IIEF score <22. Hypertension, diabetes mellitus, coronary artery disease, and smoking status were significantly associated with the ED group compared to control subjects with p values of <0.001, <0.001, 0.002 and <0.001, respectively. Overall genotype frequencies was 47 (31%) a/a, 22 (15%) a/b, 82 (55%) b/b for Intron 4 VNTR and 56 (37%) GG, 78 (52%) GT, 16 (11%) TT for the Glu298Asp polymorphism. The frequencies of Intron 4 VNTR a/a allele and Glu298Asp GT allele were associated with severe ED, while a/b and TT were associated with moderate or mild, and b/b and GG were associated with no ED. In contrast to Glu298Asp, statistically significant differences in genotypic frequencies of Intron 4 VNTR gene polymorphism between ED and control subjects was established.Abbreviations: NO: nitric oxide, NOS: nitric oxide synthase, NOS3: endothelial nitric oxide synthase, NOS2: inducible nitric oxide synthase, NOS1: neuronal nitric oxide synthase, HT: hypertension, DM: diabetes mellitus, CAD: coronary artery disease, ED: erectile dysfunction, IIEF: international index of erectile function, VNTR: variable number of tandem repeats, CDU: color doppler ultrasonography, PCR: polymerase chain reaction.

Association of MIR146A rs2910164 variation with a predisposition to sporadic breast cancer in a Pakistani cohort.

Single-nucleotide polymorphisms (SNPs) in genes coding for microRNAs (miRNAs) play a pivotal role in the progression of breast cancer (BC). We investigated the association of miR-146a rs2910164 GC polymorphism with the risk of BC in the Pakistani population. The miR-146a rs2910164 polymorphism was genotyped in 300 BC cases and 300 age- and gender-matched healthy controls using T-ARMS-PCR. Genotype and allele frequencies were calculated and the association between genotypes and the risk of BC was calculated by odds ratio (OR) and confidence interval (95%). A significant difference in genotypic frequencies (χ2 =63.10; P=<0.0001) and allelic frequencies (OR=0.3955 (0.3132-0.4993); P=<0.0001) was observed between cases and controls. Furthermore, we also found that miR-146 rs2910164 CC homozygote increased the risk of BC in the dominant (OR=0.2397 (0.1629-0.3526); P=0.0001; GG vs. GC + CC) and recessive (OR=2.803 (1.865-4.213); P=<0.0001; CC vs. GC + GG) inheritance models. In summary, miR-146a rs2910164 GC is significantly associated with BC in the Pakistani population. To our knowledge, this is the first study that assessed MIR146a rs2910164 G>C SNP in Pakistani population. By analyzing the secondary structure of MIR146A variant, a significant structural modification was noted. Study with a larger sample size is needed to further confirm of these findings.

BTNL2 gene polymorphism and sarcoid uveitis

BackgroundUveitis is a frequent and early feature of sarcoidosis. As BTNL2 (butyrophilin-like 2) gene polymorphism was found linked with the susceptibility to sarcoidosis, we investigated whether a specific genotype of...

Significance of UGT1A1*28 Genotype in Patients with Advanced Liver Injury Caused By Chronic Hepatitis C.

SummaryBackgroundChronic hepatitis C (CHC) is a significant cause of liver related morbidity and mortality worldwide. The role of genetics in the host response to hepatitis C virus is not elucidated. Genetic variations in UGT1A1 gene are the most common cause of hereditary unconjugated hyperbilirubinemia-Gilbert syndrome. This is the first study investigating the association of UGT1A1 TA repeats promoter genotypes with the degree of liver injury, viremia and biochemical markers in CHC patients with advanced liver injury and late virological relapse.MethodsGenetic testing of UGT1A1 TA repeats promoter genotypes was performed in 42 CHC patients with advanced fibrosis and cirrhosis who achieved sustained virological response and 42 healthy blood donors. CHC patients were evaluated for clinical findings, laboratory tests and imaging.ResultsUGT1A1*28 genotype (7/7 TA repeats) was observed in 23.8% CHC patients and 16.7% healthy controls with no significant difference in genotype frequencies (p=0.49). Pretreatment levels of ferritin and bilirubin were associated with the presence of UGT1A1*28 genotype, indicating its potential as a predictive marker. However, in our study, there was no correlation of UGT1A1*28 genotype with the degree of fibrosis or viremia. During antiviral treatment, dose reductions and treatment interruptions, as well as treatment success and occurrence of late virological relapse were not related to the presence of UGT1A1*28 genotype in CHC patients with severe liver injury.ConclusionsFrequencies of UGT1A1*28 genotype are high in both Serbian CHC patients and healthy subjects. The presence of UGT1A1*28 genotype was not associated with ribavirin-related adverse effects and had no effect on long term outcome in CHC patients.

MiRNA-24 Gene Sequence, DHFR -829C-T Genotypes, and Methotrexate Response in Mexican Patients with Rheumatoid Arthritis.

Aim: The present study looked for variation in the miRNA-24 sequence, and evaluated the associations between the dihydrofolate reductase (DHFR) gene-829 C-T polymorphism and plasma DHFR concentrations with response to methotrexate (MTX) treatment in Mexican patients with rheumatoid arthritis (RA).Methods: A total of 135 women with RA were classified as responders (disease activity score [DAS28] <3.2) or nonresponders to MTX (DAS28 > 3.2). We determined the genotype of the patients using the polymerase chain reaction-restriction fragment length polymorphism method. Plasma DHFR enzyme levels and mi-RNA24 sequences were assessed by enzyme-linked immunosorbent assay (ELISA) and Sanger sequencing, respectively. Allelic frequencies and the genotypic distribution of the polymorphism were analyzed by the chi-square test.Results: The genotype frequencies of the DHFR −829C-T polymorphism among responders were 37.0% CC, 52.1% CT, and 10.9% TT and for nonresponders were 33.9% CC, 56.4% CT, and 9.7% TT. No significant differences in genotype frequencies were found between the groups (p = 0.88). The DHFR levels relative to genotype for responders were 6.8 ± 2.7, 6.1 ± 2.7, and 6.5 ± 1.5 ng/mL for CC, CT, and TT, respectively, and for nonresponders were 6.5 ± 2.0, 6.1 ± 3.1, and 7.4 ± 1.8 ng/mL for CC, CT, and TT, respectively. No significant differences were found between the two groups. Similarly, both groups showed no sequence variations in miRNA-24 gene.Conclusion: The −829C-T polymorphism of DHFR gene was not associated with response to MTX by RA patients, and no variations were found in the miRNA-24 sequence that might modify the response to treatment or DHFR enzyme levels in a Mexican population with RA.

Genetic Polymorphism of HLA-G 14-bp Insertion/Deletion in Pancreas Transplant Recipients and Its Association With Type 1 Diabetes Mellitus.

Human leukocyte antigen-G is an immuno-modulatory factor that affects acute allograft rejection and autoimmune diseases such as type 1 diabetes mellitus. In this study, possible associations between human leukocyte antigen-G 14-bp insertion/deletion polymorphism and acute pancreas rejection were investigated. Human leukocyte antigen-G genotyping was assessed in 102 Iranian pancreas transplant recipients (including 41 with acute rejection and 61 with nonacute rejection). Results were compared with 100 individuals in a normal control group. No significant differences in genotype frequencies of human leukocyte antigen-G 14-bp insertion / deletion were observed in recipients who had acute rejection episodes. On the other hand, the insertion / insertion genotype was a risk factor for susceptibility to type 1 diabetes mellitus (odds ratio = 3.82, 95% confidence interval, 1.37- 11.22; P = .005). Our results provided evidence revealing that the human leukocyte antigen-G insertion / insertion genotype might be involved in the pathogenesis of type 1 diabetes mellitus.

Association of miR-146a Gene Polymorphism at loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C with Susceptibility to Kawasaki Disease in Chinese Children.

To investigate the genetic association of miR-146a gene polymorphisms at loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C in patients with Kawasaki disease (KD) and coronary artery lesions (CAL). There were 120 patients with KD and 126 healthy subjects in this study. The genotype of loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C of miR-146a gene were detected by polymerase chain reaction-sequence-based typing. For miR-146a gene polymorphisms at loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C, there were no significant difference of genotype frequencies and allele frequencies between KD group and healthy control group, or between the IVIG-resistant group and IVIG-sensitive group (P > 0.05). In KD with coronary artery lesions (KD-CAL) group, the genotype frequencies of GG were higher than that in KD without coronary artery lesion (KD-WO) group at locus rs2910164 G/C polymorphisms of miR-146a gene (χ2 = 6.660, P = 0.036), patients with KD carried genotype of GG were at 3.636 times higher risk of getting coronary artery lesions than those of non-carriers (χ2 = 6.455, P = 0.018, OR = 3.636, 95%CI = 1.280-10.262). While there was no significant difference of allele frequency of G and C between KD-CAL group and KD-WO group (P > 0.05). In KD-CAL group, the allele frequency of A was higher than that in KD-WO group at locus rs57095329 A/G polymorphisms of miR-146a gene (χ2 = 4.745, P = 0.035), carriers with allele A were at 2.422 times higher risk of getting coronary artery lesions than those of non-carriers (χ2 = 4.745, P = 0.035, OR = 2.422, 95%CI = 1.073-5.465), while there was no significant difference of genotype frequency of AA, AG, and GG types between KD-CAL group and KD-WO group (P > 0.05). There was no significant difference of genotype frequencies of TT, TC, and CC types and allele frequencies of T and C types between KD-CAL group and KD-WO group at locus rs6864584 T/C polymorphisms of miR-146a gene (P > 0.05). The significant association has been found between the genotype and allele frequency of the miR-146a gene loci rs2910164 G/C and rs57095329 A/G, the genotype GG of rs2910164 G/C, and allele A of rs57095329 A/G were risk factors for getting coronary artery lesions.

Correlation between ABCB1 gene polymorphisms, antiepileptic drug concentrations and treatment response

Abstract Aim: A possible molecular mechanism of clinically defined multidrug-resistant epilepsy involves drug efflux transporters such as P glycoprotein (P-gp), a member of the ATP-binding cassette subfamily B1 (ABCB1). We have investigated the prevalence of the C3435T, G 2677T/A, and T129C single-nucleotide polymorphisms in the promoter region of MDR1 gene, in Romanian epileptic patients. Methods: 70 epileptic patients evaluated in the Neurology Department of Cluj County Hospital were included in the study. The response to treatment was assessed by reviewing the seizure diaries and the patients were classified as responders or non-responders. Antiepileptic drug (AED) plasmatic concentrations were measured and the patients were divided into 2 groups: first group with AED concentrations in therapeutic range and the second one with sub-optimal AED concentrations. Genotyping the DNA samples, we investigated MDR1 gene polymorphism by polymerase chain reaction (PCR). Results were expressed as genotype and allele frequencies per response group and compared between subgroups. Results: 33 patients (47.14%) were classified as responders, while the remaining 37 patients (52.86%) were classified as non-responders. A comparison of responders and non-responders revealed no significant difference in genotype frequency for any of the three mutations studied. The CT heterozygote for ABCB1 T129C had significantly lower AED concentrations (p=0.041), with no significant difference for the other polymorphisms studied. Conclusions: In our study we found an association of CT variant in ABCB1 C129T with lower AED plasmatic concentrations and no association between ABCB1 variants and the drug responsiveness.

A3981 Relationship between methylenetetrahydrofolate reductase C677T gene polymorphism and left ventricular hypertrophy with hypertension

Objectives: This study was performed to explore the effects of homocysteine (Hcy) and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T on the left ventricular hypertrophy (LVH) among hypertensive Chinese Han population. Methods: This study included 456 hypertensive patients. MTHFR C677T polymorphism was analyzed by by taqman probe and fluorescent quantitative PCR. Cardiac structure and function indicators were measured by transthoracic echocardiography. According to left ventricular mass index (LVMI), 132 cases were elected out as essential hypertension with LVH group and 324 cases as non-left ventricular hypertrophy (NLVH) group. According to LVMI and left ventricular relative wall thickness (LVRWT), essential hypertension was divided into 4 subgroups: normal geometry (NG) group, concentric remodeling (CR) group, concentric hypertrophy (CH) group, and eccentric hypertrophy (EH) group. Results: (1) The frequency of TT genotype and T allele in LVH group was higher than those in NLVH group (P < 0.05). (2) The level of Hcy in TT genotype was higher than that in CT and CC genotype (P < 0.01). The values of LVMI and LVPWT in CT and TT genotype, were higher than that in CC (P < 0.01). (3) Subgroup analysis showed that there were significant differences in genotype frequency and level of Hcy among different subgroups, and highest frequency of TT genotype and highest level of Hcy were in EH group. (4) 1 umol/l increase in Hcy was associated with a 7.9% increase in the incident risk of LVH. Genetic model analysis showed that MTHFR were associated with LVH [OR 2.264 (95% CI 1.337–3.834),P = 0.002]. Conclusion: Hcy and MTHFR C677T polymorphism were an independent risk factor for LVH. TT genotype carriers or T allele carriers had a higher susceptibility to LVH incidence, especially EH.

The rs9939609 polymorphism in the fat mass and obesity associated (FTO) gene is associated with obesity in Tunisian population

Context: Variations in the fat mass and obesity-associated gene (FTO) has been associated with obesity in many populations, but the results are conflicting.Objective: The aim of this study was to evaluate the effect of the rs9939609 polymorphism in the FTO gene on obesity risk and plasma leptin, adiponectin, insulin and lipid concentrations in Tunisians.Materials and methods: Four hundred and ninety-four subjects with obesity and 334 non-obese participated in this study. The rs9939609 (T/A) genotype was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.Results: Significant differences in genotype frequencies were observed between cases and controls. In the separate analysis by gender, the association between the AA genotype and obesity was statistically significant in women but not in men. After stratification by obesity class this association remains only with obesity class III.Discussion: Our study is in agreement with studies on Caucasian, Portuguese and Cebu Filipino populations where a gender-specific association was found between rs9939609 polymorphism and obesity. It is also in agreement with studies on Mexican, Spanish and European populations, where an association was found with obesity class III.Conclusion: The rs9939609 polymorphism of FTO gene is associated with obesity, especially obesity class III in women.

Human Leukocyte Antigen class II polymorphisms among Croatian patients with type 1 diabetes and autoimmune polyglandular syndrome type 3 variant

This study included 161 patients: 92 patients had type 1 diabetes (T1D) while 69 patients had a combination of T1D and autoimmune thyroiditis, the so-called autoimmune polyglandular syndrome type 3 variant (APS3v). Those patients, as well as 93 controls, were typed for HLA-DRB1 and -DQB1 genes to assess their possible contribution to the development/protection of T1D with/without autoimmune thyroiditis. Both HLA-DRB1*04 and -DRB1*03 frequencies were significantly higher among T1D and APS3v patients than in controls. The frequencies of HLA-DRB1*11 and -DRB1*15 were lower among T1D patients, while HLA-DRB1*07 and -DRB1*11 occurred significantly less frequently among APS3v patients in comparison to controls. HLA-DQB1*03:01 and -DQB1*03:02 were associated with a higher risk of developing T1D and APS3v; HLA-DQB1*02 was significantly more present among APS3v patients while HLA-DQB1*03:03 was observed with a significantly lower frequency only among T1D patients. HLA-DRB1*03~DQB1*02 and HLA-DRB1*04~DQB1*03:02 were associated with both diseases. The higher frequency of HLA-DRB1*03/DRB1*03 among APS3v patients was the only significant difference in genotype frequency when compared to T1D patients, while high risk (HLA-DRB1*03/DRB1*04) and medium risk genotypes for T1D (HLA-DRB1*04/DRB1*04) occurred with similar frequencies in both patient groups. Although some of the results point toward shared genetic susceptibility of T1D and APS3v, observed differences in both susceptible/protective HLA profiles indicate the necessity of further studies in order to elucidate the pathogenesis of these diseases.

Association of APOB and LIPC polymorphisms with type 2 diabetes in Chinese Han population

BackgroundApolipoprotein B (APOB), and hepatic lipase (LIPC) genes have been shown to play a key role in lipid metabolism in type 2 diabetes (T2D). This study aimed to investigate the association of the three polymorphisms (rs679899 in APOB and rs6078 and rs6083 in LIPC) with T2D and related clinical quantitative traits. MethodsWe conducted a case-control study in Chinese Han population, with a total of 929 T2D patients and 1044 healthy subjects in Chinese Han population. Polymorphisms were genotyped by MassARRAY Genotyping System. ResultsThe risk allele G of the polymorphism rs679899 was related to T2D (odds ratio (OR): 1.207, 95% confidence interval (CL): 1.006–1.448, P = 0.043) and the polymorphism rs679899 was associated with glutamyl transpeptidase (GGT) levels (P = 0.001). We also showed that the polymorphism rs6083 was associated with cholesterol (CHOL) levels (P = 0.012), triglyceride (TG) levels (P = 0.040), and low-density lipoprotein cholesterol (LDL) levels (P = 0.033). No significant difference in genotypic frequencies of rs6078 and rs6083 was observed between T2D patients and controls. ConclusionThis study suggests that the APOB polymorphism rs679899 is associated with type 2 diabetes and GGT levels, while the LIPC polymorphism rs6083 may influence CHOL, TG, and LDL levels in Chinese Han population.

Correlations between SIRT1 gene polymorphisms and diabetic kidney disease

To investigate the correlations between SIRT1 gene polymorphisms and diabetic kidney disease (DKD). There were 150 patients with DKD in the observation group (urinary albumin excretion rate (UAER) ≥ 300 mg 24 h−1), and 160 patients with a more than 10 year history of type 2 diabetes but without retinopathy and DKD (UAER < 30 mg 24 h−1) in the control group. Genotypes of three tagged single-nucleotide polymorphism loci (rs3818292, rs4746720 and rs10823108) in the SIRT1 gene in the two groups were detected. Risks of DKD for patients with the GG and GG + AG genotype in the rs10823108 locus of the SIRT1 gene were 2.96 and 2.92 times higher than that for AA genotype carriers, respectively. The risk of DKD for patients with the GG genotype in the rs3818292 locus was 0.23 times and 0.21 times higher than that for AA and for AA + AG genotype carriers, respectively, and the risk of DKD for patients with allele G was 0.66 times higher than that for allele A carriers. There was no significant difference in genotype frequency of rs4746720 locus gene polymorphisms between the observation and control groups. The SIRT1 gene is a genetic susceptibility gene of DKD. Mutation genotype GG and GG + AG in the rs10823108 locus can increase the risk of DKD. Mutation genotype GG and allele G in the rs3818292 locus can decrease the risk of DKD.

Anatomical and molecular studies of cytochrome P450 family CYP7A1 gene polymorphism and its association with gallstone in north Indian population

IntroductionIn this study, we have mainly focused on the molecular and biochemical aspects to know the cause of gall stone diseases in human. To know about these problems, there may be necessitating initiating interest in researchers of this field and to set up easily available tools and techniques. The screening of polymorphism with molecular approaches of P450 super family CYP7A1 gene was performed to explore its relation with gallstone diseases. MethodsTotal 300 samples (150 patients and 150 controls) were analyzed for the study. The polymorphisms were analyzed by PCR followed by RFLP with BsaI restriction enzyme. The lipid profile was estimated by using modified Roeschlau’s method. The cholesterol content in gall stones was determined with Liebermann-Burchard reaction method. ResultsThe cholesterol content of recovered gallstones was found 98.86±25.43 (% by weight). BMI and serum glucose were found higher in patients than in the control group: 30.84±8.13kg/m2vs 28.61±7.50kg/m2 (P=0.032), and 121.03±15.11mg/dL vs 104±21.05mg/dL (P=0.001) respectively. Statistical analysis showed no significant differences in genotypic frequencies of gene CYP7A1 gene polymorphism between patients and controls. Frequencies of C allele (CYP7A1 gene polymorphism) in patients and controls were obtained 24.24% vs 26.46% (P=0.621, OR=0.89). Genotypic frequencies between patients and controls were found 59.42% vs 54.97% for AA; 30.25% vs 34.72% for CA; and 10.33% vs 10.31 for CC. DiscussionIn this study by using of multiple logistic regression analysis the results have indicated that CYP7A1 gene polymorphism may not play any significant role in gallstone disease.

C677T and A1298C polymorphisms of methylene tetrahydrofolate reductase in non-Hodgkin lymphoma: southeast Iran.

Polymorphisms of the methylene tetrahydrofolate reductase (MTHFR) gene have been reported as risk factors for non-Hodgkin lymphoma (NHL) in some populations. Our goal was to evaluate the potential role of A1298C and C677T polymorphisms of MTHFR in risk of NHL in southeast Iran. In the present case-control study, 127 patients with newly diagnosed NHL along with 150 ethnicity- and age-matched controls were examined. The A1298C and C677T polymorphisms were genotyped using the Tetra Amplification Refractory Mutation System polymerase chain reaction method. There were no significant differences in genotype frequencies between cases and controls regarding either A1298C polymorphism. For this polymorphism, 53.8% of the controls and 54.3% of the patients with NHL showed homozygous wild-type (AA) genotype. Variant 1298C allele was recognized with overall frequency of 34.6% in both groups. Frequencies of CC, CT, and TT genotypes of C677T polymorphism were observed in 73.1%, 25.8%, and 1.3% of the controls, and 64.5%, 33.1%, and 2.4% of the patients with NHL (p>0.05). In combination, CT + TT conferred a significantly higher risk of NHL (odds ratio [OR] 1.5, 95% confidence interval [CI] 0.9-2.4, p = 0.03). Overall, variant 677T allele presented with higher frequency in the patients with NHL than the controls (26.7% versus 21.3%, respectively; OR 1.3, 95% CI 0.8-2.1, p>0.05). Although statistically insignificant, the highest risk of NHL was identified in patients with C677T; A1298C: CT; CC haplotype (OR 4.7, 95% CI 0.4-46.4, p = 0.1). Combination of CT and TT genotypes of C677T polymorphism conferred a significantly higher risk for NHL. It is recommended to investigate further the potential role of this polymorphism in NHL development.