Characteristic of the genetic variability of four polymorphic variants (rs2069705, rs17880053, rs11126176, and rs804271) in representative samples of indigenous and arrived populations of Siberia

Russian Journal of Genetics - The variability of potentially important functional polymorphic variants rs2069705 (5'UTR of the IFNG gene), rs17880053 (near 5'UTR of the IFNGR2), rs11126176...     

PVT1 (rs13281615) and miR-146a (rs2910164) polymorphisms affect the prognosis of colon cancer by regulating COX2 expression and cell apoptosis

In this study, we aimed to investigate the potential correlation between rs13281615/rs2910164 polymorphisms and the prognosis of colon cancer (CC). Taqman was utilized to genotype the rs13281615/rs2910164 polymorphisms in recruited subjects. Kaplan–Meier survival curves were calculated to study the prognostic values of different genotypes of rs13281615/rs2910164 polymorphisms. Real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays were conducted to establish a potential signaling pathway underlying the role of rs13281615/rs2910164 polymorphisms, whereas bioinformatics analysis and luciferase reporter assays were performed to identify plasmacytoma variant translocation 1 (PVT1) and cyclooxygenase-2 (COX2) as targets of microRNA-146a (miR-146a). No significant difference was observed in respect to clinical characteristics among subjects with different genotypes. However, patients genotyped as GG/CC + GC showed the lowest chance of survival, whereas patients of GA + AA/GG genotype showed the highest chance of survival. Moreover, the relative expressions of PVT1, prostaglandin E2 (PGE2), and COX2 were the lowest and the relative expression of miR-146a was the highest in GA + AA/GG subjects, validating the roles of PVT1, miR-146a, and COX2 in CC. In addition, both PVT1 and COX2 were identified as virtual targets of miR-146a, and the luciferase activities of cells cotransfected with wild-type PVT1/COX2 and miR-146a mimics were significantly reduced. Moreover, the presence of PVT1 decreased the level of miR-146a whereas increasing the messenger RNA and protein levels of COX2, thus establishing a PVT1/miR-146a/COX2 signaling pathway underlying the pathogenesis of CC. The presence of rs13281615 G > A polymorphism on PVT1 and the rs2910164 C > G polymorphism on miR-146a contributes to a favorable prognosis in CC patients via modulating the activity of the PVT1/miR-146a/COX2 signaling pathway.     

Alcohol Dehydrogenase-1B (rs1229984) and Aldehyde Dehydrogenase-2 (rs671) Genotypes Are Strong Determinants of the Serum Triglyceride and Cholesterol Levels of Japanese Alcoholic Men

Background

Elevated serum triglyceride (TG) and high-density-lipoprotein cholesterol (HDL-C) levels are common in drinkers. The fast-metabolizing alcohol dehydrogenase-1B encoded by the ADH1B*2 allele (vs. ADH1B*1/*1 genotype) and inactive aldehyde dehydrogenase-2 encoded by the ALDH2*2 allele (vs. ALDH2*1/*1 genotype) modify ethanol metabolism and are prevalent (≈90% and ≈40%, respectively) in East Asians. We attempted to evaluate the associations between the ADH1B and ALDH2 genotypes and lipid levels in alcoholics.

Methods

The population consisted of 1806 Japanese alcoholic men (≥40 years) who had undergone ADH1B and ALDH2 genotyping and whose serum TG, total cholesterol, and HDL-C levels in the fasting state had been measured within 3 days after admission.

Results

High serum levels of TG (≥150 mg/dl), HDL-C (>80 mg/dl), and low-density-lipoprotein cholesterol (LDL-C calculated by the Friedewald formula ≥140 mg/dl) were observed in 24.3%, 16.8%, and 15.6%, respectively, of the subjects. Diabetes, cirrhosis, smoking, and body mass index (BMI) affected the serum lipid levels. Multivariate analysis revealed that the presence of the ADH1B*2 allele and the active ALDH2*1/*1 genotype increased the odds ratio (OR; 95% confidence interval) for a high TG level (2.22 [1.67–2.94] and 1.39 [0.99–1.96], respectively), and decreased the OR for a high HDL-C level (0.37 [0.28–0.49] and 0.51 [0.37–0.69], respectively). The presence of the ADH1B*2 allele decreased the OR for a high LDL-C level (0.60 [0.45–0.80]). The ADH1B*2 plus ALDH2*1/*1 combination yielded the highest ORs for high TG levels and lowest OR for a high HDL-C level. The genotype effects were more prominent in relation to the higher levels of TG (≥220 mg/dl) and HDL-C (≥100 mg/dl).

Conclusions

The fast-metabolizing ADH1B and active ALDH2, and especially a combination of the two were strongly associated with higher serum TG levels and lower serum HDL-C levels of alcoholics. The fast-metabolizing ADH1B was associated with lower serum LDL-C levels.     

PSCA gene variants (rs2294008 and rs2978974) confer increased susceptibility of gallbladder carcinoma in females

Background and aim

PSCA is a tissue specific tumor suppressor or oncogene which has been found to be associated with several human tumors including gallbladder cancer. It is considered to be involved in the cell-proliferation inhibition and/or cell-death induction activity. Therefore, we aimed to investigate the role of PSCA gene polymorphisms in gallbladder cancer risk in North Indian population.

Methodology

A total of 405 gallbladder cancer patients and 247 healthy controls were included in the case–control study for risk prediction. We examined the association of two functional SNPs, rs2294008 and rs2978974 in PSCA gene by genotyping using Taqman allelic discrimination assays. Statistical analysis was done using SPSS software, version 17. Linkage disequilibrium and haplotype analysis was done with the help of SNPstats software. FDR test was used to correct for multiple comparisons.

Results

No significant associations of rs2294008 and rs2978974 genetic variants of the PSCA gene were found with GBC risk at allele, genotype or haplotype levels. Stratifying the subjects on the basis of gallstone also did not show any significant result. However, on gender stratification, we found a significant association of T_rs2294008-G_rs2978974 haplotype with higher risk of GBC in females (FDR Pcorr = 0.021, OR = 1.6). In contrary, T_rs2294008-A _rs2978974 haplotype conferred significant lower risk in males (FDR Pcorr = 0.013; OR = 0.25).

Conclusions

These findings suggest that PSCA genetic variants may have a significant effect on GBC susceptibility in a gender specific manner.     

Association of C-reactive protein (CRP) rs1205 and rs2808630 variants and risk of cancer

The correlation between rs1205, rs2808630 variants of C-reactive protein (CRP) gene and susceptibility of cancer has been assessed previously, but with conflicting results. We adopted odds ratios (ORs) with 95% confidence intervals (CIs), in silico tools and enzyme-linked immunosorbent assay (ELISA) analysis to evaluate this association. Totally, 10,614 cancer subjects and 33,294 controls were involved in the pooled analysis. When all the studies were pooled, no significant correlation was indicated between the two variants and cancer risk. However, in stratification analysis by ethnicity, we found that CRP rs1205 C>T polymorphism was associated with an elevated risk of cancer in Asians (T-allele vs. C-allele, OR = 1.20, 95% CI = 1.06–1.36, p_{heterogeneity} = .226; TT vs. CC, OR = 1.48, 95% CI = 1.14–1.93, p_{heterogeneity} = .089). Similar findings were observed for rs2808630 variant. In silico tools showed that lung adenocarcinoma participants with high CRP expression may have shorter overall survival time than low expression group. ELISA analysis indicated that CRP expression in prostate adenocarcinoma subjects with TT + TC genotypes was statistically higher than in those with CC genotypes. CRP rs1205 C>T and rs2808630 T>C polymorphism may be associated with cancer risk, especially for Asians.     

The Association between Four Genetic Variants in MicroRNAs (rs11614913, rs2910164, rs3746444, rs2292832) and Cancer Risk: Evidence from Published Studies

MicroRNAs (miRNAs) participate in diverse biological pathways and may act as either tumor suppressor genes or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNA may contribute to cancer development with changes in the microRNA''s properties and/or maturation. Polymorphisms in miRNAs have been suggested in predisposition to cancer risk; however, accumulated studies have shown inconsistent conslusionss. To further validate determine whether there is any potential association between the four common SNPs (miR-196a2C>T, rs11614913; miR-146aG>C, rs2910164; miR-499A>G, rs3746444; miR-149C>T, rs2292832) and the risk for developing risk, a meta-analysis was performed according to the 40 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the extent of the association. The results demonstrated that the rs11614913TT genotype was significantly associated with a decreased cancer risk, in particular with a decreased risk for colorectal cancer and lung cancer, or for Asian population subgroup. In addition, the rs2910164C allele was associated with decreased risk for esophageal cancer, cervical cancer, prostate cancer, and hepatocellular carcinoma (HCC), in particular in Asian population subgroup. Similarly, the rs3746444G allele was observed as a risk factor for cancers in the Asian population. It is concluded that two SNPs prsent in miRNAs(rs11614913TT, and rs2910164C) may protect against the pathogenesis of some cancers, and that the rs3746444 may increase risk for cancer.     

Association between Fibrillin1 Polymorphisms (rs2118181, rs10519177) and Transforming Growth Factor β1 Concentration in Human Plasma

Transforming growth factor (TGF)-β1 is a cytokine that participates in a broad range of cellular regulatory processes and is associated with various diseases including aortic aneurysm. Increased TGF-β1 levels are linked to Marfan syndrome (MFS) caused by fibrillin1 (FBN1) mutations and subsequent defects in signaling system. FBN1 single nucleotide polymorphisms (SNPs) rs2118181 and rs1059177 do not cause MFS but are associated with dilative pathology of aortic aneurysms (DPAAs). TGF-β1 and FBN1 SNPs rs2118181 and rs1059177 are potential biomarkers for early diagnosis of DPAA. We investigated the relationship between TGF-β1 levels in human blood plasma and FBN1 rs2118181 and rs1059177 in 269 individuals. The results showed a quantitative dependence of SNP genotype and TGF-β1 concentration. Presence of a single rs2118181 minor allele (G) increased the amount of TGF-β1 by roughly 1 ng/mL. Two copies of FBN1 rs1059177 minor allele (G) were required to have an additive effect on TGF-β1 levels. We found higher TGF-β1 concentrations in men compared with women (p = 0.001). A strong correlation between TGF-β1 levels and FBN1 SNPs suggests that a single nucleotide substitution in FBN1 sequence might reduce bioavailability or binding properties of fibrillin-1 and have an effect on TGF-β1 activation and cytokine concentration in blood plasma. By establishing the relationship between TGF-β1 and FBN1 SNPs rs2118181 and rs1059177, we provide evidence that their combination might be used as molecular biomarkers to identify patients at risk for sporadic ascending aortic aneurysm and aortic dissection.     

Polymorphisms of fibronectin-1 (rs3796123; rs1968510; rs10202709; rs6725958; and rs35343655) are not associated with bronchopulmonary dysplasia in preterm infants

Molecular and Cellular Biochemistry - Bronchopulmonary dysplasia (BPD) is a chronic lung disease that mainly affects premature newborns. Many different factors, increasingly genetic, are involved...     

Prostaglandin Endoperoxide H Synthase-2 (PGHS-2) Variants and Risk of Obesity and Microvascular Dysfunction Among Tunisians: Relevance of rs5277 (306G/C) and rs5275 (8473T/C) Genetic Markers

The purpose of this study was to determine the impact of six PGHS-2 genetic variants on obesity development and microvascular dysfunction. The study included 305 Tunisian subjects (186 normal weights, 35 overweights and 84 obeses). PCR analyses were used for allelic discrimination between polymorphisms. Prostaglandin (PGE2, PGI2), leptin, and matrix metalloproteinase (MMP1, 2, 3, 9) levels were evaluated by ELISA. Fatty acid composition was performed by gas chromatography–mass spectrometry. Our results revealed that subjects carrying the PGHS-2 306CC (rs5277) and 8473CC (rs5275) genotypes present higher anthropometric values compared to wild-type genotypes (306GG, BMI (Kg/m²): 27.11?±?0.58; WC (cm): 93.09?±?1.58; 306CC, BMI: 33.83?±?2.46; WC: 109.93?±?5.41; 8473TT, BMI: 27.75?±?0.68; WC: 93.96?±?1.75; 8473CC, BMI: 33.72?±?2.2; WC: 117.89?±?2.94). A reduced microvascular reactivity and a higher PGE2 level were also found in individuals with the 306CC and 8473CC genotypes in comparison to 306GG and 8473TT carriers (306GG, Peak Ach-CVC (PU/mmHg): 0.46?±?0.03; PGE2 (pg/ml): 7933.1?±?702; 306CC, Peak Ach-CVC: 0.24?±?0.01; PGE2: 13,380.3?±?966.2; 8473TT, Peak Ach-CVC: 0.48?±?0.05; PGE2: 7086.41?±?700.31; 8473CC, Peak Ach-CVC: 0.23?±?0.01; PGE2: 13,175.7?±?1165.8). Fatty acid analysis showed a significant increase of palmitic acid (PA) (34.2?±?2.09 vs. 16.82%?±?1.76, P?<?0.001), stearic acid (SA) (25.76?±?3.29 vs. 9.05%?±?2.53, P?<?0.001), and linoleic acid (LA) (5.25?±?1.18 vs. 0.5%?±?0.09, P?<?0.001) levels in individuals carrying the PGHS-2 306CC genotype when compared to GG genotype individuals. Subjects with the 8473CC genotype showed also a significant increase of PA, SA ,and LA levels when compared to TT genotype carriers (PA: 38.02?±?1.51 vs. 12.65%?±?1.54, P?<?0.001; SA: 32.96?±?1.87 vs. 1.38%?±?0.56, P?<?0.001; LA: 26.84?±?2.09 vs. 3.7%?±?1.54, P?<?0.001). Logistic regression analysis revealed that PGHS-2 306CC and 8473CC variants are significantly associated with obesity status (OR 6.25, CI (1.8–21.6), P?=?0.004; OR 3.01, CI (1.13–8.52), P?=?0.03, respectively). Haplotypes containing the C₃₀₆:T₈₄₇₃ (OR 2.91; P?=?0.01) and G_306:C₈₄₇₃ (OR 5.25; P?=?0.002) combinations were associated with an enhanced risk for obesity development in the studied population. In conclusion, our results highlight that PGHS-2 306G/C and 8473T/C variants could be useful indicators of obesity development, inflammation, and microvascular dysfunction among Tunisians.

     

Association of genetic variants rs641153 (CFB), rs2230199 (C3), and rs1410996 (CFH) with age-related macular degeneration in a Brazilian population

This study aimed to investigate the association among genetic variants of the complement pathway CFB R32Q (rs641153), C3 R102G (rs2230199), and CFH (rs1410996) with age-related macular degeneration (AMD) in a sample of the Brazilian population. In a case-control study, 484 AMD patients were classified according to the clinical age-related maculopathy grading system (CARMS) and compared to 479 unrelated controls. The genetic variants rs1410996 of complement H (CFH), rs641153 of complement factor B (CFB), and rs2230199 of complement 3 (C3) were evaluated through polymerase chain reaction (PCR) and direct sequencing. The associations between single nucleotide polymorphisms (SNPs) and AMD, adjusted by age, were assessed by using logistic regression models. A statistically significant association was observed between AMD risk and rs2230199 variant with an OR of 2.01 (P  = 0.0002) for CG individuals compared to CC individuals. Regarding the comparison of advanced AMD versus the control group, the OR was 2.12 (P = 0.0036) for GG versus AA genotypes for rs1410996 variant. Similarly, the OR for rs2230199 polymorphism was 2.3034 (P  = 5.47^e-05) when comparing CG individuals to CC carriers. In contrast, the rs641153 variant showed a significant protective effect against advanced AMD for GA versus GG genotype (OR = 0.4406; P  = 0.0019). When comparing wet AMD versus controls, a significant association was detected for rs1410996 variant (OR = 2.16; P  = 0.0039) comparing carriers of the homozygous GG versus AA genotype, as well as in the comparisons of GG (OR = 3.0713; P  = 0.0046) and CG genotypes (OR = 2.2249; P  = 0.0002) versus CC genotype for rs2230199 variant, respectively. The rs641153 variant granted a significant protective effect against wet AMD for GA versus GG genotypes (OR = 0.4601; P  = 0.0044). Our study confirmed the risk association between rs2230199 and rs1410996 variants and AMD, and the protective role against AMD for rs641153 variant.     

Association between rs4673 (C/T) and rs13306294 (A/G) haplotypes of NAD(P)H oxidase p22phox gene and severity of stenosis in coronary arteries

Phagocytic NADH/NADPH oxidase is an important enzyme producing reactive oxygen species within subendothelial space of vessels. Findings have shown that p22phox subunit is an essential element related to the enzyme activity. Since some p22phox polymorphisms are thought to have functional roles in the enzyme thus, we studied the association between rs4673 (C242T) and rs13306294 (A/G) haplotypes and the severity of stenosis in coronary arteries. One hundred eighty-two subjects undergoing coronary angiography were recruited on the base of study design. Patients (n=114) had at least a stenosed coronary artery (>50% stenosis) and subdivided into three subgroups; SVD (n=28), 2VD (n=31) and 3VD (n=55) while controls (n=68) had the normal coronary arteries (<5% stenosis). The direct haplotyping technique of SNPs was performed using ARMS-RFLP-PCR method. Furthermore, alphabet-based tools predicted the changes of secondary structure at the rs4673 position. All haplotypes being proposed theoretically were found in the study population. The distribution of two-allele haplotypes had no significant difference between patients and controls (P=0.1). Although the rs4673 allele frequency was not significant between the groups (P>0.5), chi square test and multinomial regression analysis showed an observed high risk for rs13306294 A allele among patients. The bioinformatics tools predicted that the p22phox secondary structure is not changed due to the substitution of Tyr→His at the rs4673 position. We concluded that the polymorphisms have no allele linkage on the chromosome. In addition, the rs13306294 A allele is a potential factor of stenosis of coronary arteries that increases susceptibility for the extent of disease.     

Influence of b2 adrenergic receptor polymorphism (rs1042713 and rs1042714) on anthropometric,hormonal and lipid profiles in polycystic ovarian syndrome

BackgroundPolycystic ovarian syndrome (PCOS) is a frequently encountered disorder. This study aimed to identify polymorphisms in ADRB2 in Saudi PCOS development and to study its influence on lipids, hormones, and anthropometric parameters.MethodsSaudi females (100) suffering from PCOS and healthy controls (100) were investigated. The estimation of cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), plasma glucose, leptin Insulin, and ghrelin were carried out. The DNA was extracted, and ADRB2 fragment carrying the exon 1 was amplified and sequenced.ResultsThe waist, W/H ratio, lipids, glucose, and insulin were significantly higher in the obese PCOS compared to the normal weight group. The leptin and ghrelin were not different. Two single nucleotide polymorphisms (SNPs): rs1042713 (Arg16Gly; A>G) and rs1042714 (Gln27Glu; C>G) were identified. The genotype and allele frequency of rs1042713 did not differ in the total PCOS and normal weight, and obese PCOS compare to the controls. However, rs1042714 was significantly associated with PCOS development, where the minor G allele was protective against PCOS development.ConclusionsThe rs1042714 polymorphism of the ADRB associates with PCOS development in Saudis, while rs1042713 does not. However, the GG genotype of rs1042713 associates significantly with elevated BMI, waist, hip, W/H, and leptin, and decreased ghrelin. On the other hand, rs1042714 genotypes do not associate with any abnormality except the homozygous GG have higher triglycerides and lower HDL-C. Interestingly, glucose showed different correlation patterns in individuals carrying different genotypes of the two studied SNP, indicating clearly that the metabolic responses to a normal nutrient are significantly influenced by the genotypes of the SNPs in ADRB2.     

Association of nicotinamide-N-methyltransferase (NNMT) gene rs694539 variant with bipolar disorder

Here we report the association of the rs694539 variant of nicotinamide-N-methyltransferase gene with bipolar disorder in a case–control study of 95 bipolar disorder patients and 201 healthy controls (χ² = 13.382, P = 0.001). With the polymerase chain reaction restriction fragment length polymorphism method we developed we were able to show the association for the first time. This new finding may provide evidence to understand the mechanism of the disease.     

A Combination of CD28 (rs1980422) and IRF5 (rs10488631) Polymorphisms Is Associated with Seropositivity in Rheumatoid Arthritis: A Case Control Study

IntroductionThe aim of the study was to analyse genetic architecture of RA by utilizing multiparametric statistical methods such as linear discriminant analysis (LDA) and redundancy analysis (RDA).MethodsA total of 1393 volunteers, 499 patients with RA and 894 healthy controls were included in the study. The presence of shared epitope (SE) in HLA-DRB1 and 11 SNPs (PTPN22 C/T (rs2476601), STAT4 G/T (rs7574865), CTLA4 A/G (rs3087243), TRAF1/C5 A/G (rs3761847), IRF5 T/C (rs10488631), TNFAIP3 C/T (rs5029937), AFF3 A/T (rs11676922), PADI4 C/T (rs2240340), CD28 T/C (rs1980422), CSK G/A (rs34933034) and FCGR3A A/C (rs396991), rheumatoid factor (RF), anti–citrullinated protein antibodies (ACPA) and clinical status was analysed using the LDA and RDA.ResultsHLA-DRB1, PTPN22, STAT4, IRF5 and PADI4 significantly discriminated between RA patients and healthy controls in LDA. The correlation between RA diagnosis and the explanatory variables in the model was 0.328 (Trace = 0.107; F = 13.715; P = 0.0002). The risk variants of IRF5 and CD28 genes were found to be common determinants for seropositivity in RDA, while positivity of RF alone was associated with the CTLA4 risk variant in heterozygous form. The correlation between serologic status and genetic determinants on the 1st ordinal axis was 0.468, and 0.145 on the 2nd one (Trace = 0.179; F = 6.135; P = 0.001). The risk alleles in AFF3 gene together with the presence of ACPA were associated with higher clinical severity of RA.ConclusionsThe association among multiple risk variants related to T cell receptor signalling with seropositivity may play an important role in distinct clinical phenotypes of RA. Our study demonstrates that multiparametric analyses represent a powerful tool for investigation of mutual relationships of potential risk factors in complex diseases such as RA.     

Distinct Role of CD86 Polymorphisms (rs1129055, rs17281995) in Risk of Cancer: Evidence from a Meta-Analysis

Background and Purpose

Previous studies concerning the role of CD86 polymorphisms (rs1129055 and rs17281995) in cancer fail to provide compelling evidence. The aim of this study was to investigate the role of common polymorphisms in the risk of cancer by meta-analysis.

Methods

By using the search terms Cluster of Differentiation 86/CD86/B7-2/polymorphism/polymorphisms/cancer, we searched PubMed, Embase, CNKI, and Wanfang and identified four studies for rs1129055 (2137 subjects) and rs17281995 (2856 subjects) respectively. Cancer risk was estimated by odds ratio (OR) and 95% confidence interval (95% CI).

Major Findings

Overall, we observed significant reduced risk of cancer in relation to rs1129055. Compared with the individuals with AA genotype, the individuals with GG genotype appeared to have 62% decreased risk to develop cancer (GG versus AA: OR, 0.62; 95% CI, 0.49–0.79; P_het., 0.996). Similar effects were indicated in the G versus A allele model and the GG versus GA+AA genetic model (OR, 0.83; 95% CI, 0.74–0.93; P_het., 0.987; OR, 0.63; 95% CI, 0.50–0.79; P_het., 0.973). In addition, we found genotypes of rs17281995 had a major effect on overall cancer risk (CC versus GG: OR, 2.38; 95% CI, 1.43–3.95; P_het., 0.433; C versus G: OR, 1.23; 95% CI, 1.06–1.43; P_het., 0.521; CC versus GC+GG: OR, 2.38; 95% CI, 1.45–3.93; P_het., 0.443). The association was also observed in Caucasians and colorectal cancer. No obvious publication bias was detected in this meta-analysis.

Conclusions

These data reveal that rs1129055 may have protective effects on cancer risk in Asians and that rs17281995 is likely to contribute to risk of cancer, particularly colorectal cancer in Caucasians.     

Association study of rs10768683 and rs968857 polymorphisms with transfusion-dependent thalassemia (TDT) in a southern Iranian population

Previous studies reported that detection of polymorphisms inherited through paternal model could be potential markers for the Non-Invasive Prenatal Diagnosis (NIPD) of β-thalassemia. The aim of the current study was to find out the associations of rs10768683 and rs968857 with transfusion-dependent thalassemia (TDT) in a southern Iranian population. A total of 175 subjects were investigated, divided into patients with TDT as case group (n?=?75) and healthy people as control group (n?=?100). Genomic DNAs were extracted from peripheral blood using salting out procedure. Genotyping rs10768683 and rs968857 was carried out by ARMS-PCR, then statistical analyses were assessed using SPSS, and Medcalc ver. 18 software. Data showed that rs10768683 was statistically significant in co-dominant model of inheritance (P?=?0.025, OR?=?2.11 [1.08-4.15]) and genotype frequencies of CG among controls and cases were 0.68 and 0.80, respectively. However, according to genotype frequencies, there was no association between rs968857 and TDT among cases and healthy controls in any models of inheritance. In conclusion, the present study showed the association of rs10768683 with major β-thalassemia through ARMS-PCR technique.     

Polycystic ovary syndrome is linked with the fat mass obesity (FTO) gene variants rs17817449 and rs1421085 in western Saudi Arabia

Polycystic ovary syndrome (PCOS) is characterised by infertility, obesity, insulin resistance and clinical and/or biochemical signs of hyperandrogenism. Obesity is known to be correlated with PCOS causing ovulatory dysfunction and hormone imbalances. Moreover, fat mass and the obesity gene (FTO) were linked with obesity and PCOS. Therefore, it is of interest to determine the genotype and allele frequency for three FTO variants - rs17817449 (G/T), rs1421085 (C/T) and rs8050136 (A/C) -in western Saudi population. 95 PCOS patients and 94 controls were recruited for this study. The genetic variants were assayed using real-time polymerase chain reaction using TaqMan genotyping assays. The chi-squared test was applied to investigate the difference between single nucleotide polymorphisms on PCOS and control subjects, and binary logistic regression was used to determine the association of FTO variants with PCOS symptoms. Variants rs17817449 and rs1421085 were significantly linked with PCOS susceptibility in the study population. Rs17817449 and rs8050136 were significantly associated with hair loss in the PCOS group. Furthermore, rs1421085 and rs8050136 were associated with a high body mass index (BMI>30 kg/m2). Risk alleles in our population associated with hair loss and elevated BMI in women with PCOS were homozygous C for rs8050136. This data will help in defining the genetic predisposition of PCOS among women in western Saudi Arabia.     

Effects of VRK2 (rs2312147) on White Matter Connectivity in Patients with Schizophrenia

Recent genome-wide association studies of schizophrenia reported a novel risk variant, rs2312147 at vaccinia-related kinase 2 gene (VRK2), in multiple Asian and European samples. However, its effect on the brain structure in schizophrenia is little known. We analyzed the brain structure of 36 schizophrenia patients and 18 healthy subjects with regard to rs2312147 genotype groups. Brain magnetic resonance scans for gray matter (GM) and white matter (WM) analysis, and genotype analysis for VRK2 rs2312147, were conducted. The Positive and Negative Syndrome Scale and the Digit Symbol Test were assessed for schizophrenia patients. There was no significant difference in either GM volume or WM connectivity with regard to rs2312147 genotype in healthy subjects. In contrast, we found significant differences in the WM connectivity between rs2312147 CC and CT/TT genotype groups of schizophrenia patients. The related brain areas included the splenium of corpus callosum, the left occipital lobe WM, the internal capsule (left anterior limb and right retrolenticular part), the bilateral temporal lobe WM, the left fornix/stria terminalis, the left cingulate gyrus WM, and the left parietal lobe WM. Voxelwise correlation analysis revealed that the Digit Symbol Test scores (age corrected) correlated with the fractional anisotropy in WM tracts that previously showed significant group differences between the CT/TT and CC genotypes in the rs2312147 CT/TT genotype group, while no significant correlation was found in the CC genotype group. Our data may provide evidence for the effect of VRK2 on WM connectivity in patients with schizophrenia.