TG Genotype Research Articles

The Association of prolactin receptor gene polymorphism with recurrent miscarriage in a sample of Iraqi women

Recurrent miscarriage (RM) is a common occurrence, about 15% of all clinically recognized pregnant women resulting in pregnancy failure. RM has been inconsistently defined. When defined as 3 consecutive pregnancy losses prior to 20 weeks from the last menstrual period, it affects about (1- 2) % of women. our study study whether the polymorphisms in PRL-R gene are correlated with the risk of RM. RM casas was (n=25) and apparently healthy control subject (n=15), were enrolled genotyping of PRL-R gene SNP (rs37389 G>T) polymorphism were determined by using Taqman genotyping assay. This study was carried out in the laboratory of institute of genetic angering and biotechnology for postgraduate study- university of Baghdad from November 2018 to February 2019, and the sample were collected from several laboratories in Baghdad. the distribution of genotypes and alleles frequencies results showed that at rs37389‎ SNP of PRL-R gene, as related with TT, TG and combined TG+GG genotypes, significant differences in frequency percentage were recorded between RM patients and apparently healthy subjects, the frequency of wild TT genotype was significantly lower in patients with RM than in apparently healthy subjects. In contrast, the frequency of heterozygous TG genotype and mutant genotype were significant higher in patients with RM compared with apparently healthy subjects. This study found an association between both heterozygous and homozygous mutants genotype at rs37389 of PRL-R gene with a risk for RM susceptibility.

IKZF1 Rs4132601 Polymorphism and Susceptibility to Acute Lymphocytic Leukemia in Children: A Meta-analysis.

Many studies have shown that IKAROS family zinc finger 1 (IKZF1) rs4132601 polymorphism is strongly linked to acute lymphoblastic leukemia (ALL) in children, but their conclusions have been inconsistent. This meta-analysis is set out to investigate the association between IKZF1 rs4132601 polymorphism and its susceptibility to childhood ALL. On the basis of inclusion criteria, PubMed, EMBASE, Web of Science, CNKI, China Wanfang, VIP, and other databases were searched from the time of the establishment of the library database to December 2019 for all case-control studies. Stata 15.0 was applied for meta-analysis to calculate the combined odds ratio (OR) value and 95% confidence interval (CI) of each genotype at IKZF1 rs4132601. Subgroup analysis done by ethnicity, sensitivity analysis, and publication bias assessment was further performed. Nine pieces of literature was included in this meta-analysis, including 2281 children with ALL and 2923 controls. There were significant differences in the allelic model (T vs. G: combined OR=0.75, 95% CI: 0.68-0.82, P<0.05) in both Asian and Caucasian children. In addition to this, there were statistically significant differences in the dominant, homozygous and heterozygous genetic model in both Asian and Caucasian children. The difference was significant in the recessive genetic model (TT vs. TG+GG: combined OR=0.75, 95% CI: 0.67-0.84) in Caucasian children, but not in Asian children (combined OR=0.85, 95% CI: 0.70-1.04, P>0.05). There is a strong correlation between IKZF1 rs4132601 polymorphism and ALL in children. Compared with the G allele, T alleles can lower the risk of childhood ALL, and TT, TT+TG and TG genotypes can also reduce the risk of ALL in children.

CD33 rs3865444 as a risk factor for Parkinson’s disease

BackgroundAlzheimer’s (AD) and Parkinson’s diseases (PD) share a few elements of their clinical, pathological and genetic backgrounds. The CD33 rs3865444 has emerged as a strong genetic locus associated with AD through genome-wide association study (GWAS). However, little is known for its role in PD. ObjectiveTo assess the role of CD33 rs3865444 on PD risk. MethodsWe genotyped 358 patients with PD and 358 healthy controls for theCD33 rs3865444. Odds ratios (ORs) with the respective 95% confidence intervals (CIs)], were calculated with the SNPStats software, assuming five genetic models (co-dominant, dominant, recessive, over-dominant and log-additive), with the G allele as the reference allele. ResultsThe CD33 rs3865444 was associated with decreased PD risk in the dominant [GG vs GT + TT; OR (95% CI) = 0.61 (0.45−0.82), p = 0.001], the over-dominant [GG + TT vs GT; OR (95% CI) = 0.65 (0.48−0.89), p = 0.0061], log-additive [OR (95% CI) = 0.67 (0.52−0.86), p = 0.0014], and co-dominant [with overall p = 0.0043, and OR (95% CI) = 0.62 (0.45−0.84) for the TG genotype compared to the GG], modes of inheritance. ConclusionsThe CD33 rs3865444 is associated with decreased PD risk, and larger studies investigating the role of CD33 rs3865444 on PD are needed.

Contribution of rs3211938 polymorphism at CD36 to glucose levels, oxidized low-density lipoproteins, insulin resistance, and body mass index in Mexican mestizos with type-2 diabetes from western Mexico

Background: type-2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance (IR), and abnormal fatty acid metabolism in which the CD36 receptor has been implicated in glucose and lipid dysregulation. Objective: to evaluate the contribution of polymorphism CD36 rs3211938 to metabolic profile in T2DM Mexican mestizos from western Mexico. Methods: we included 115 individuals classified as non-T2DM (NT2DM) adults and T2DM patients. Polymorphism CD36 rs3211938 was assessed by PCR-RFLP. Anthropometric and metabolic markers were measured by routine methods, and insulin and oxidized LDL (ox-LDL) were measured by ELISA. Results: the distribution of genotypes between NT2DM and T2DM patients was different (p < 0.001), as was the allele frequency (p = 0.002). NT2DM TG carriers showed the lowest levels of basal insulin and HOMA-IR index in comparison with TT carriers (p < 0.05 and p < 0.05, respectively). In the T2DM group TG carriers showed high BMI, WHR, and weight values (p = 0.001; p ≤ 0.05 and p < 0.05, respectively), and the highest levels of basal glucose, HDL-cholesterol, ox-LDL, and HOMA-IR (p < 0.001; p < 0.001; p < 0.001, and p = 0.001, respectively) in comparison with diabetic TT carriers. Conclusion: the CD36 rs3211938 TG genotype is associated with high levels of glucose, ox-LDL, HDL-cholesterol, and IR, and with increased BMI in Mexican mestizo T2DM patients from western Mexico.

Evaluation of Vitamin D-Binding Protein Gene Polymorphism and its Plasma Concentration in Kurdish Patients With Breast Cancer in Sanandaj, Iran

Background: Several studies have indicated that polymorphism in vitamin D pathway genes is associated with breast cancer (BC) risk. Vitamin D-binding protein (VDBP) is a vital element in the metabolism of the vitamin D. VDBP carries the serum 25(OH) D3 to cells to promote vitamin D biological functions, such as cell proliferation and apoptosis. Missense SNP (rs.7041) is a common polymorphism in VDBP gene, which shows ethnic-specific allele frequencies. Objectives: This study presents the correlation of the rs7041 (Asp432Glu) gene polymorphism and plasma concentrations of VDBP in Kurdish patients with BC in Sanandaj, Iran. Methods: This cross-sectional study included 44 premenopausal BC patients and 44 healthy subjects. Plasma VDBP concentration was measured by enzyme-linked immunosorbent assay (ELISA). The VDBP (rs7041) was genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Results: VDBP level was associated with a non-significant risk of BC (P=0.397). Frequencies of individuals with VDBP (rs7041) TT, TG, and GG genotypes were 13.6%, 52.2%, and 34.09% in case group and 11.3%, 79.5%, and 9.9% in control group, respectively. Genotype GG associated with increased susceptibility to developing BC (odds ratio [OR]=5.172, CI: 1.555-17.2, P=0.007). There was a significant reverse correlation between GT genotype and BC (OR=0.282, 95% CI: 0.110-0.722, P=0.008) Conclusion: The changes in the vitamin D pathway may increase susceptibility to develop BC in the Iranian Kurdish population.

Association of Long Non-Coding RNA Polymorphisms with Gastric Cancer and Atrophic Gastritis.

Long non-coding RNAs (lncRNA) play an important role in the carcinogenesis of various tumours, including gastric cancer. This study aimed to assess the associations of lncRNA ANRIL, H19, MALAT1, MEG3, HOTAIR single-nucleotide polymorphisms (SNPs) with gastric cancer and atrophic gastritis. SNPs were analyzed in 613 gastric cancer patients, 118 patients with atrophic gastritis and 476 controls from three tertiary centers in Germany, Lithuania and Latvia. Genomic DNA was extracted from peripheral blood leukocytes. SNPs were genotyped by the real-time polymerase chain reaction. Results showed that carriers of MALAT1 rs3200401 CT genotype had the significantly higher odds of atrophic gastritis than those with CC genotype (OR-1.81; 95% CI 1.17–2.80, p = 0.0066). Higher odds of AG were found in a recessive model (CC vs. TT + CT) for ANRIL rs1333045 (OR-1.88; 95% CI 1.19–2.95, p = 0.0066). Carriers of ANRIL (rs17694493) GG genotype had higher odds of gastric cancer (OR-4.93; 95% CI 1.28–19.00) and atrophic gastritis (OR-5.11; 95% CI 1.10–23.80) compared with the CC genotype, and carriers of HOTAIR rs17840857 TG genotype had higher odds of atrophic gastritis (OR-1.61 95% CI 1.04–2.50) compared with the TT genotype; however, the ORs did not reach the adjusted significance threshold (p < 0.007). In summary, our data provide novel evidence for a possible link between lncRNA SNPs and premalignant condition of gastric cancer, suggesting the involvement of lncRNAs in gastric cancer development.

Single Nucleotide Polymorphism of IL-2 Gene at Position +166 in Type 1 Diabetes of Iraqi Patients

The present study aimed at investigating of frequency of polymorphism of interleukin-2 gene (IL2) at position+166 SNP) in Type 1 Diabetes and in healthy controls subjects 39 of Iraqi patients, (12 males &amp; 27 females;1 5.65 ± 1.79 years) and 21 controls.(7 mail &amp; 14 female ; 14.66 ± 3.43 years) attended the hospital in Baghdad for diagnosis and treatment during the period February 2015 – January 2016 were enrolled in this study, the polymorphism of IL2+166 was data waved by polymerase chain reaction-specific sequence primer (PCR-SSP) assay. The results showed a comparison IL2+166 genotypes &amp; alleles between T1D patients &amp; controls frequencies of TT genotype &amp; T allele (71.69vs. 68.95%;P =0.589 respectively) There was a significant increase in patients contrast to controls, (51.38vs. 48.08%; P =0.312) and associated RR rates were 19.2% &amp; 27.0%, respectively. And the related EF values were 1.56 &amp; 1.60 .Similar observations were made in GG genotype. In contrast TG genotype &amp; G allele (23.93 vs. 28.55%,P =1.000 respectively) Low frequency was observed in patients compared to healthy subjects (43.28 vs. 43.22%; P =0.312), and the related PF values were 0.56 &amp; 0.62 , respectively. The results of the study indicate that IL2+166 SNP may have a role in the mechanism of etiopathogenic of T1D in the samples of Iraqi patients

Single Nucleotide Polymorphism of IL-2 Gene at Position +166 in Type 1 Diabetes of Iraqi Patients

The present study aimed at investigating of frequency of polymorphism of interleukin-2 gene (IL2) at position+166 SNP) in Type 1 Diabetes and in healthy controls subjects 39 of Iraqi patients, (12 males &amp; 27 females;1 5.65 ± 1.79 years) and 21 controls.(7 mail &amp; 14 female ; 14.66 ± 3.43 years) attended the hospital in Baghdad for diagnosis and treatment during the period February 2015 – January 2016 were enrolled in this study, the polymorphism of IL2+166 was data waved by polymerase chain reaction-specific sequence primer (PCR-SSP) assay. The results showed a comparison IL2+166 genotypes &amp; alleles between T1D patients &amp; controls frequencies of TT genotype &amp; T allele (71.69vs. 68.95%;P =0.589 respectively) There was a significant increase in patients contrast to controls, (51.38vs. 48.08%; P =0.312) and associated RR rates were 19.2% &amp; 27.0%, respectively. And the related EF values were 1.56 &amp; 1.60 .Similar observations were made in GG genotype. In contrast TG genotype &amp; G allele (23.93 vs. 28.55%,P =1.000 respectively) Low frequency was observed in patients compared to healthy subjects (43.28 vs. 43.22%; P =0.312), and the related PF values were 0.56 &amp; 0.62 , respectively. The results of the study indicate that IL2+166 SNP may have a role in the mechanism of etiopathogenic of T1D in the samples of Iraqi patients

The association of tumor necrosis factor alpha, lymphotoxin alpha, tumor necrosis factor receptor 1 and tumor necrosis factor receptor 2 gene polymorphisms and serum levels with periodontitis and type 2 diabetes in Serbian population

ObjectivesAiming to show that periodontitis (PD) and type 2 diabetes (T2D) are bidirectionally related and potentially linked by inflammatory cytokines, we searched for association between −308 G/A Tumor necrosis factor-alpha (TNFα), +252A/G Lymphotoxin-alpha (LTα), +36A/G Tumor necrosis factor receptor 1 (TNFR1) and +676 T/G tumor necrosis factor receptor 2 (TNFR2) single nucleotide polymorphisms (SNPs) and: risk of PD or PD + T2D; periodontitis parameters in PD and PD + T2D; serum levels of cytokines/their receptors. Relationship between periodontal inflammation and serum cytokine/receptor levels was also assessed. DesignSubjects were stratified as: 57 healthy controls (HC); 58 PD; 65 PD + T2D. Sociodemographic, environmental, behavioral and periodontal clinical data were recorded. SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism, while cytokines/receptors levels were quantified by enzyme-linked immunosorbent assay. Impact of periodontal inflammation was measured using periodontal inflamed surface area (PISA). ResultsTNFα AA genotype showed protective effect in T2D + PD compared to PD, even adjusted for behavioral/environmental factors (OR 0.18; 95 %CI 0.037−0.886; p = 0.035). LTα AG heterozygotes had increased risk of PD (OR 3.27; 95 %CI 1.35−7.96; p = 0.016), while TNFR2 TG genotype had protective effect (OR = 0.44; 95 %CI 0.954−0.9794; p = 0.043). TNFR1 AA was predictor of periodontal pocket depth and clinical attachment loss in PD. Correlation between TNFR2 concentration and PISA was negative in PD, positive in PD + T2D. ConclusionsNone of the SNPs showed cross-susceptibility between PD and T2D. + 252A/G LTα and +676 T/G TNFR2 SNPs are associated with PD risk. Periodontal destruction in healthy individuals is influenced by TNFR1 genotype. Impact of periodontal on systemic inflammation is masked by T2D.

The EDN2 rs110287192 gene polymorphism is associated with paratuberculosis susceptibility in multibreed cattle population.

Paratuberculosis (pTB), also known as Johne's disease (JD), is a contagious, chronic, and granulomatous inflammatory disease of the intestines of ruminants which is caused by Mycobacterium avium subsp. paratuberculosis (MAP) infection, resulting in billions of dollars in economic losses worldwide. Since, currently, no effective cure is available for MAP infection, it is important to explore the genetic variants that affect the host MAP susceptibility. The aim of this study was to analyze a potential association between EDN2 synonymous gene mutations (rs110287192, rs109651404 and rs136707411), that modifies susceptibility to pTB. EDN2 rs110287192, rs109651404 and rs136707411 mutations were genotyped in 68 infected and 753 healthy animals from East Anatolian Red crossbred, Anatolian Black crossbred and Holstein breed cattle by using Custom TaqMan SNP Genotyping Assays. For pTB status, serum antibody levels S/P ≥ 1.0 were assessed in carriers of the different EDN2 genotypes. EDN2 rs110287192 mutation showed a significant association with bovine pTB (adj. p < 0.05). For rs110287192 locus, the odd ratios for GG and TG genotypes versus TT genotypes were 1.73; (95% CI = 0.34-8.59) and 0.53 (95% CI = 0.12-2.37) respectively, which indicated that proportion of TG heterozygotes were significantly higher in control animals as compared to pTB animals. On the other hand, while rs136707411 mutation showed a suggestive association with pTB status in the examined cattle population (nominal p < 0.05); no association was detected between rs109651404 genotypes and pTB status. Selecting animals against rs110287192-GG genotype may decrease the risk of pTB in cattle of the Bos taurus taurus subspecies.

STAT3 gene polymorphism in chronic obstructive pulmonary disease.

The aim of this study was to explore the correlation between rs8069115, rs41289087, and rs11079042 polymorphisms of the signal transducer and activator of transcription 3 (STAT3) gene and chronic obstructive pulmonary disease (COPD). A total of 200 patients diagnosed with COPD were enrolled in the disease group. Meanwhile, 200 normal subjects were selected as the control group. Peripheral blood was collected from subjects in the disease group and control group. Subsequently, nucleated cells were isolated for determination of STAT3 gene polymorphisms. Quantitative Polymerase Chain Reaction (qPCR) was utilized to detect the expression level of STAT3. Samples from 12 patients with differences in STAT3 haplotypes and 12 cases with no difference were collected and treated with transcriptome sequencing to analyze pathways enriched with differentially expressed genes. There were statistically significant differences in allele distributions at rs8069115 between the disease group and control group (p=0.000), and the allele frequency of G was higher in disease group. Genotype distributions of rs8069115 (p=0.000) and rs41289087 (p=0.000) of the STAT3 gene in disease group were significantly different in comparison with the control group. The frequency of rs8069115 GG genotype was remarkably higher, while the frequency of rs41289087 TG genotype was lower in the disease group (p<0.05). In addition, compared with the control group, the distributions of the dominant model (p=0.002) and recessive model (p=0.004) of rs8069115 of the STAT3 gene were markedly different in the disease group. A significantly higher frequency of dominant model GG+GA and lower frequency of recessive model GA+AA were observed at rs8069115 in the disease group (p<0.05). Moreover, the haplotype distributions of AGC (p=0.002), ATC (p=0.001), GTA (p=0.010), and GTC (p=0.035) at rs8069115, rs41289087, and rs11079042 were different between the disease group and control group. Besides, rs8069115 locus and rs11079042 locus were linked to each other (D'=0.523). There was a remarkable association between rs11079042 polymorphism of the STAT3 gene and gene expression (p<0.05). STAT3 was highly expressed in patients with genotype CC (p<0.05). Furthermore, changes in transcriptome levels among different haplotype populations (haplotype with different distributions vs. haplotype with no difference in distribution) were analyzed. The results demonstrated that multiple pathways, such as ECM-receptor interactions, cell cycle checkpoints, and protein processing were notably enriched (p<0.05). According to our results, we confirmed that the polymorphisms (rs8069115, rs41289087, and rs11079042) of STAT3 gene are noticeably correlated with the occurrence and progression of COPD.

Association of strong risk of hTERT gene polymorphic variants to malignant glioma and its prognostic implications with respect to different histological types and survival of glioma cases.

Germline genetic variants of human telomerase reverse transcriptase (hTERT) are known to predispose for various malignancies, including glioma. The present study investigated genetic variation of hTERT T/G (rs2736100) and hTERT G/A (rs2736098) with respect to glioma risk. Confirmed cases (n = 106) were tested against 210 cancer-free healthy controls by the polymerase chain reaction-restriction fragment length polymorphism technique for genotyping. Homozygous variant 'GG' genotype of rs2736100 frequency was > 4-fold significantly different in cases versus controls (39.6% 17.2%; p < 0.0001). Furthermore, variant 'G' allele was found to be significantly associated with cases (0.5 versus 0.2 in controls; p < 0.0001). Homozygous variant rs2736098 'AA' genotype (35.8% versus 23.8%) and allele 'A' (0.49 versus 0.34) showed a marked significant difference in cases and controls, respectively (p < 0.05). In hTERT rs2736100, the GG genotype significantly presented more in higher grades and GBM (p < 0.0001). Furthermore, the GG variant of hTERT rs2736100 had a poor probability with respect to the overall survival of patients compared to TG and TT genotypes (log rank p = 0.03). Interestingly, two haplotypes of hTERT rs2736100/rs2736098 were identified as GG and GA that conferred a > 3- and 5-fold risk to glioma patients respectively, where variant G/A haplotype was observed to have the highest impact with respect to glioma risk (p < 0.0001). The results of the present study indicate that hTERT rs2736098 and rs2736100 variants play an important role in conferring a strong risk of developing glioma. Furthermore, hTERT rs2736100 GG variant appears to play a role in the bad prognosis of glioma patients. Haplotypes GG and GA could prove to be vital tools for monitoring risk in glioma patients.

The TP63 Gene Polymorphism rs17506395 is Associated with Early Breast Cancer in Cameroon.

Background:Breast cancer (BC) is a leading female cancer worldwide and cause of cancer-related death, especially in developing countries. Genetic predispositions to BC development in African population is poorly studied, and meanwhile the SNP rs17506395 in TP63 gene locus has been associated with the development of breast cancer in Asian women, no investigation has been undertaken within African population. We investigated the impact of this polymorphism in a representative African population. Methods:We undertook a case-control study including 335 women, of which 111 were breast cancer patients and 224 controls. Using blood-derived germline DNA, PCR-RFLP was used to investigate the polymorphism of TP63 gene at rs17506395 locus. Unconditional logistic regression was used to study the association between the TP63 gene polymorphism and risk of BC development. After stratification into different age and ethno-linguistic groups as well as menopausal status, the Cochran-Mantel-Haenszel test was used to measure significance of the associations. Results:Comparing cases with controls, no significant associations between genotype and disease development was observed. Similarly, when cases were stratified according to menopausal status and ethno-linguistic groups, no significant association was observed between genotype and disease development. However, in women of 40 years and below, TT and TG genotypes were associated with breast cancer development. The minor G allele seems to protective against early breast cancer onset OR of 0.5 (95%CI = 0.26-0.94, p = 0.03). Conclusion:Our data revealed an association between rs15706395 and the risk of early breast cancer onset. The GG genotype seems to reduce the risk of early breast cancer. Larger studies are needed to confirm the potential of this SNP as biomarker for breast cancer prognostic.

Adiponectin and leptin gene variants and their effects on body weight trajectories in children from birth to 6 years of age: the PREDI Study.

Excess body weight confers a high risk to human health. Body weight variation between subjects can be partially explained by genetic differences. The aim of the present study was to investigate the association of genetic variants in the ADIPOQ (rs2241766) and LEP (rs7799039) genes with body weight trajectories in children from birth to 6 years of age. This was a prospective cohort (PREDI Study). Socio-economic, biological and anthropometric data were collected at four time points: at birth in the maternity unit; 1-2, 4-5 and 6 years old at the participants' homes. Genotyping was performed by PCR-restriction fragment length polymorphism. Poisson regression and linear mixed-effect regression models were used to address the association of ADIPOQ and LEP genotypes with BMI. Excessive body weight at pre-pregnancy (β = 0·339, P = 0·01) and excessive gestational weight gain (β = 0·51, P < 0·001) were associated with children's BMI trajectory from birth to 6 years. The ADIPOQ-rs2241766 TG or GG genotype was associated with a higher risk of excess body weight in the first 6 years of life (both sexes relative risk 1·25, 95 % CI 1·01, 1·56; female relative risk 1·67, 95 % CI 1·20, 2·31). BMI increased over the years according to the presence of the TG or GG genotype (β = 0·01, 95 % CI 0·01, 0·02), particularly in females (β = 0·02, 95 % CI 0·01, 0·04). The ADIPOQ-rs2241766 TG and GG genotypes increased the risk of excess body weight in children from birth to 6 years of age and had a positive effect on body weight trajectories in girls. The LEP-rs7799039 genetic variant was not associated with body weight trajectory in children.

Association Between Ghrelin Gene Polymorphism and Cerebral Infarction.

BackgroundThe aim of this study was to explore the associations of ghrelin gene polymorphisms at rs26312, rs26802 and rs27647 with cerebral infarction.Material/MethodsA total of 200 cerebral infarction patients in our hospital were enrolled as the disease group, while 200 healthy people were enrolled as the control group. Peripheral venous blood was collected from both groups, and the ghrelin gene polymorphisms at rs26312, rs26802, and rs27647 in nucleated cells were detected through sequencing.ResultsThe genotype distribution at ghrelin gene loci rs26802 and rs27647 in the disease group was significantly different from that in the control group. The distribution of recessive model at ghrelin gene locus rs26802 in the disease group was different from that in the control group, in which the TG+GG frequency was evidently higher in the disease group. The AA genotype at ghrelin gene locus rs26312 was remarkably associated with the ghrelin gene expression level, and the expression level of ghrelin gene in the disease group was remarkably lower than that in the control group. The genotype at ghrelin gene locus rs26312 was associated with activated partial thromboplastin time (APTT), and APTT was significantly shorter in patients with GG genotype. The genotype at ghrelin gene locus rs26802 was associated with D-dimer, and the D-dimer level was significantly lower in patients with TG genotype. The genotype at ghrelin gene locus rs27647 was associated with prothrombin time (PT), and PT was obviously shorter in patients with TT genotype.ConclusionsThe ghrelin gene polymorphisms are remarkably associated with the occurrence of cerebral infarction.

Comprehensive analysis of the effect of rs2295080 and rs2536 polymorphisms within the mTOR gene on cancer risk.

There is still no conclusion on the potential effect of the rs2295080 and rs2536 polymorphisms of mTOR (mammalian target of rapamycin) gene on different cancers. Herein, we performed a comprehensive assessment using pooled analysis, FPRP (false-positive report probability), TSA (trial sequential analysis), and eQTL (expression quantitative trait loci) analysis. Eighteen high-quality articles from China were enrolled. The pooled analysis of rs2295080 with 9502 cases and 10,965 controls showed a decreased risk of urinary system tumors and specific prostate cancers [TG vs. TT, TG+GG vs. TT and G vs. T; P<0.05, OR (odds ratio) <1]. FPRP and TSA data further confirmed these results. There was an increased risk of leukemia [G vs. T, GG vs. TT, and GG vs. TT+TG genotypes; P<0.05, OR>1]. The eQTL data showed a potential correlation between the rs2295080 and mTOR expression in whole blood samples. Nevertheless, FPRP and TSA data suggested that more evidence is required to confirm the potential role of rs2295080 in leukemia risk. The pooled analysis of rs2536 (6653 cases and 7025 controls) showed a significant association in the subgroup of “population-based” control source via the allele, heterozygote, dominant, and carrier comparisons (P<0.05, OR>1). In conclusion, the TG genotype of mTOR rs2295080 may be linked to reduced susceptibility to urinary system tumors or specific prostate cancers in Chinese patients. The currently data do not strongly support a role of rs2295080 in leukemia susceptibility. Large sample sizes are needed to confirm the potential role of rs2536 in more types of cancer.

KRAS gene polymorphism (rs61764370) and its impact on breast cancer risk among women in kerala population, South India

Background: In association with the risk of developing different types of cancer, several studies have currently reported association of single-nucleotide polymorphisms in the lethal-7 miRNA binding site within the 3'-untranslated region of KRAS gene. The present study was conducted for assessing the role of KRAS gene polymorphism (rs61764370 T >G) and its impact on breast cancer (BC) risk among the Kerala population, South India. Subjects and Methods: A case–control study was conducted at two health-care centers in Kerala, South India, involving 112 BC patients and 112 healthy controls (females). Genetic analysis was performed to detect KRAS polymorphism (rs61764370 T >G) employing polymerase chain reaction–restriction fragment length polymorphism method. Odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the relationship of KRAS (rs61764370) polymorphism with BC susceptibility. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS, version 21.0) software and MedCalc software (version 16.4.3). Results: The frequency distribution of KRAS (rs61764370) polymorphism was found to be different between case and control groups significantly indicating that the KRAS gene could play an important role in the pathogenesis of BC in South Indian population. The rs61764370 TG genotype (OR = 1.59; 95% CI = 0.87–2.92; P = 0.02), GG genotype (OR = 3.177; 95% CI = 1.34–7.48; P = 0.008), as well as the G allele (OR = 2.45; 95% CI = 1.32–4.57; P = 0.004) was found to increase the risk of BC among the studied South Indian population. Conclusion: The present study provided evidence regarding the role of KRAS polymorphism (rs61764370) in developing BC among the studied population. The KRAS rs61764370 variant was found to increase the BC risk among the South Indian population (Kerala). Further studies using larger sample sizes in different ethnicities are warranted to confirm the study findings.

Pri-miR-144 rs9279 is associated with type 2 diabetes and regulation of stress response.

Single-nucleotide polymorphisms (SNPs) of microRNAs (miRNAs) may alter miRNA expression, binding affinity, and/or messenger RNA expression levels of the target genes, thus leading to disease susceptibility. This study explored the association between SNPs in neuroendocrine stress response-related miRNAs and type 2 diabetes (T2D). In the screening stage, the association between six candidate SNPs of miRNAs and T2D was analyzed in a case-control study including 504 T2D cases and 494 healthy controls. Homozygous GG genotype of pri-miR-144 rs9279 showed significant association with increased risk of T2D compared with homozygous TT genotype (adjusted odds ratio [OR] = 1.62, 95% confidence interval [CI]: 1.07-2.45; p = .023) and the combined TT/TG genotype (adjusted OR = 1.59, 95% CI: 1.08-2.36; p = .020). In the validation stage, the association was further validated in a second independent set of subjects. The GG genotype showed consistent directions and effect sizes that were identified in previous additive and recessive models. The expression levels of miRNAs were further compared between different genotypes in the 179 newly diagnosed cases and 183 frequency-matched healthy controls. As a result, the GG genotype carriers had significantly upregulated expression of plasma miR-144 and cortisol, as compared to individuals with TT and TG genotypes, respectively, in total subjects and subgroups (p < .05). Eventually, NR3C1 was proved to be a stress-related target gene of miR-144, indicating that pri-miR-144 rs9279 may contribute to the development of T2D by altering regulation of stress response.

Evaluation of TP53 Codon 72, P21 Codon 31, and MDM2 SNP309 Polymorphisms in Iranian Patients with Acute Lymphocytic Leukemia.

The tumor suppressing protein p53 and its downstream effector p21 play important roles in cell cycle regulation. Deficiency or deactivation of these proteins as a result of gene alterations has been indicated in several cancers. Such genetic variations could be considered as susceptibility indicators in acute lymphocytic leukemia (ALL). Therefore, we investigated the associations between ALL risk and TP53 codon 72, p21 codon 31, and MDM2 SNP309 polymorphisms in an Iranian population. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the MDM2 T309G (rs2279744), TP53 codon Arg72Pro (rs1042522), and p21 Ser31Arg (rs1801270) single nucleotide polymorphisms (SNPs). This study was performed in 115 ALL patients and 115 healthy controls in Khuzestan province in southwest Iran. In the control group and ALL patients, p21 Ser/Arg, and MDM2 TG and GG genotypes were associated with significant 1.81-fold (95% confidence interval CI= 1.008-3.267; P < 0.05), 11.07-fold (95% CI= 5.10-24.05; P < 0.0001), and 19.41-fold (95% CI= 8.56-43.99; P < 0.0001) increased risks for ALL, respectively. The TP53 72 Arg allele was significantly more prevalent in ALL patients (56.96%) than in control subjects (47.39%), and was significantly associated with ALL (OR= 1.47; 95% CI = 1.017-2.121, P < 0.05). The MDM2T309G and the p21 Ser31Arg SNPs indicate a significantly increased risk for developing ALL in Khuzestan province.

A novel T177P missense variant in the HSPA8 gene associated with the low tolerance of Awassi sheep to heat stress.

This study was conducted to identify the association of coding variations in the HSPA8 gene with heat stress in two different breeds of sheep. All the coding regions of the HSPA8 gene of Awassi and Arabi sheep were covered by amplifying nine exons. A single-strand conformation polymorphism (SSCP) was utilized to assess the genetic variations in both breeds. The possible association of the observed genotypes with rectal temperature (RT), respiratory rate (RR), and heat tolerance coefficient (HTC) was analyzed in different seasons. While all the coding regions of both sheep were monomorphous, a remarkable heterogeneity was observed in exon 4, of which two SSCP patterns, a normal TT and a mutant TG, were detected. The TG genotype was characterized by a missense variant of T177P with frequencies of 77% in Awassi and 54% in Arabi. Cumulative in silico tools indicated extremely deleterious consequences for T177P on protein structure, function, and stability. Results indicated that sheep with the TT genotype had significantly (P< 0.05) lower RT, RR, and HTC values than sheep with the TG genotype. Therefore, a significant association of T177P with a lower tolerance of Awassi to higher temperature conditions was revealed. In conclusion, the identified T177P may have damaging effects in the HSPA8, which affects the ability of Awassi sheep to cope up with elevated temperatures compared with Arabi sheep. This manuscript describes a novel description of a highly deleterious missense variant in the HSPA8 gene that may reduce the ability of sheep to withstand high-temperature conditions.