Genetic variants in epoxide hydrolases modify the risk of oligozoospermia and asthenospermia in Han-Chinese population

Objectives

Epoxide hydrolases are involved in detoxifying and excreting the environmental chemicals, which are associated with decreased semen quality and male infertility. We hypothesized that polymorphisms in epoxide hydrolases may be associated with risk of oligozoospermia and asthenospermia.

Design and methods

In this study, 468 fertile controls and 672 idiopathic male infertile patients were recruited. SNPstream and TaqMan assay were used to genotype four single nucleotide polymorphisms in EPHX1 and EPHX2. The semen analysis was performed by computer-assisted semen analysis system.

Results

Our results demonstrated that rs1042064 of EPHX2 was significantly associated with decreased risk of oligozoospermia (OR = 0.65, 95% CI: 0.44–0.98) and asthenospermia (OR = 0.66, 95% CI: 0.46–0.94).

Conclusions

Our results provided evidence that genetic variants in epoxide hydrolases may modify the risk of oligozoospermia and asthenospermia in Han-Chinese population.     

Interleukin-23 receptor genetic variants contribute to susceptibility of multiple cancers

Aim

Interleukin-23 (IL-23) and IL-23 receptor (IL23R) play an important role during the T-helper 17 (Th17) cell-mediated inflammatory process as well as pathogenesis of multiple cancers. Several IL-23R single nucleotide polymorphisms (SNPs), especially rs6682925, rs10889677 and rs1884444 polymorphisms, are considered to have significant impacts on susceptibility of multiple cancers. A number of case-control studies have explored the role these genetic polymorphisms in development of carcinogenesis, but the conclusions are inconsistent. Therefore, we conducted this meta-analysis to systematically investigate the associations between the three genetic variants and multiple cancer risk.

Methods

A total of ten studies are eligible (12,211 patients and 14,650 controls). Pooled odds ratios (ORs) and the 95% confidence interval (95% CI) were appropriately calculated using either fixed-effect model or random-effect model.

Results

Significant associations between rs6682925 or rs10889677 polymorphism and cancer risk were found (OR = 1.11, 95% CI = 1.03–1.21, P = 0.007; or OR = 0.85, 95% CI = 0.71–0.92, P = 0.001). However, there was no such association between rs1884444 genotypes and cancer susceptibility (P > 0.05).

Conclusion

These findings reveal that the IL-23R rs6682925 and rs10889677 genetic variants play a more important part in pathogenesis of multiple cancers.     

CYP2C9 genotype and association with bone mineral density: A pilot study

Background

In recent years reduced bone mineral density (BMD) and osteoporosis have become major public health problems. Single nucleotide polymorphisms (SNPs) in the cytochrome P450 2C9 (CYP2C9) gene influence the response to oral anticoagulant drugs, which are positively associated with the risk to develop osteoporosis. The aim of the present investigation was to clarify a potential role of CYP2C9 sequence variations and susceptibility to develop osteoporosis.

Subjects and methods

Ninety two consecutive angiologic outpatients, mean age: 60.3 ± 14.4, without secondary causes of bone loss were genotyped and classified as patients with normal BMD, osteopenia and osteoporosis according to WHO criteria by dual-energy X-ray absorptiometry at the lumbar spine and/or the femoral neck. Potential association between the CYP2C9 genotype and BMD was tested.

Results

59% of the patients (n = 54) presented with reduced BMD and were compared to 38 age-matched persons with normal BMD. The genotype distribution showed 15% heterozygous for CYP2C9*2 p.Arg144Cys, 14% for CYP2C9*3 p.IIe359Leu, 2% for both polymorphisms, and 69% had wildtype genotypes. Patients with CYP2C9 mutations had significantly lower BMD values at the femoral neck and displayed a four-fold higher adjusted risk to suffer from reduced BMD than individuals with wildtype genotypes (p = 0.02).

Discussion

Oral anticoagulant treatment is common in angiologic outpatients. The gene variants CYP2C9*2 and CYP2C9*3 have been shown to require lower maintenance doses of oral anticoagulant drugs. An association between oral anticoagulant drugs and the susceptibility to develop osteoporosis in relation to sequence variations in the CYP2C9 gene is suggested to be mediated via the glucocorticoid synthesis pathway.

Conclusion

The CYP2C9*2/CYP2C9*3 variants were significantly associated with femoral BMD in a selected elderly Austrian population. These variants could contribute to the complex risk to develop osteoporosis.     

Klotho gene polymorphism of rs3752472 is associated with the risk of urinary calculi in the population of Han nationality in Eastern China

Background/aims

The incidence of urolithiasis has considerably increased throughout the world in the last two decades. Clinical researches have showed an association between oxidative stress and stone formation. Emerging evidence indicated a novel function for klotho protein in anti-oxidative stress. In this study, we aimed at investigating a possible relationship between klotho gene polymorphisms and the risk of calcium oxalate urolithiasis in the population of Han nationality in Eastern China.

Methods

Klotho gene polymorphisms rs3752472 in exon3, rs650439 in intron 4 and rs577912 in intron 1 were investigated in 426 patients with calcium oxalate stones compared with 282 age-matched healthy volunteers with no history of stone formation, using TaqMan SNP Genotyping Assays.

Results

Significant differences were found between rs3752472 and the risk of nephrolithiasis as CC genotype of rs3752472 klotho polymorphism had almost 2-fold increased stone risk compared with the heterozygote genotype CT and homozygous genotype TT(95% CI = 1.013–2.255, OR = 1.512,p = 0.043).

Conclusion

Our results showed that the rs3752472 polymorphism of klotho gene is associated with the risk of calcium oxalate urolithiasis and may act as a risk factor during stone formation in our study population.     

Genetic polymorphisms in the DNA repair gene XRCC1 and susceptibility to glioma in a Han population in northeastern China: A case–control study

Background

Several single nucleotide polymorphisms (SNPs) in the X-ray cross-complementing group 1 (XRCC1) gene have been shown to influence DNA repair and to modify cancer susceptibility. To investigate the role of these loci further, we examined the association of three XRCC1 polymorphisms with the risk of gliomas in a Han population in northeastern China.

Methods

Using a PCR–RFLP method, XRCC1 Arg194Trp, Arg280His and Arg399Gln were genotyped in 624 glioma patients and 580 healthy controls.

Results

Significant differences in the distribution of the Arg399Gln allele were detected between glioma patients and healthy controls by a logistic regression analysis (OR = 1.35, 95%CI 1.17–1.68, P = 0.001). Our data also revealed that the Arg399Gln variant (allele A) carriers had an increased glioma risk compared to the wild-type (allele G) homozygous carriers (OR = 1.40, 95%CI 1.12–1.76, P = 0.003).

Conclusions

These results suggest that the XRCC1 Arg399Gln might influence the risk of developing glioma in a Han population in northeastern Chinese.     

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.     

Three single nucleotide variants of the HDAC gene are associated with type 2 diabetes mellitus in a Chinese population: A community-based case–control study

Objectives

There are no data regarding the possible role of the single nucleotide polymorphism (SNP) of class I histone deacetylases (HDACs) in type 2 diabetes mellitus (DM). We designed this study to examine whether polymorphisms of HDACs can be implicated in that disease.

Methods

A community-based, case–control study was conducted, with a total of 568 subjects (284 patients and 284 controls) enrolled. Four polymorphisms of HDAC1 (rs1741981) and HDAC3 (rs11741808, rs2547547, rs2530223) were examined by the use of TaqMan technology.

Results

We found a significant association with risk of type 2 DM for three SNPs of HDAC3, including rs11741808 [odds ratio (OR) = 0.53, 95% confidence interval (CI): 0.35–0.81], rs2547547 [OR = 1.72, 95% CI: 1.13–2.64], and rs2530223 [OR = 1.39; 95% CI: 1.01–1.91]. Subgroup analysis showed that BMI ≥ 23 kg/m², high triglyceride and high blood pressure, together with the rs11741808AG genotype, were associated with a significantly decreased risk for type 2 DM, with ORs of 0.50 (95% CI: 0.27–0.91), 0.38 (95% CI: 0.20–0.71) and 0.43 (95% CI: 0.24–0.76) compared with the AA genotype, respectively. In a population with normal total cholesterol, the AG genotype yielded a significantly decreased risk of type 2 DM risk, with an OR of 0.42 (95% CI: 0.25–0.70) when compared with the persons of the AA genotype. For rs2547547, in a population with normal total cholesterol and triglyceride, the AG genotype was associated with a significantly increased risk of type 2 DM, with ORs of 1.92 (95% CI: 1.17–3.15) and 2.24 (95% CI: 1.28–3.94) when compared with the population carrying the AA genotype.

Conclusions

The results suggest that variants of HDAC3 contribute to an increased prevalence of type 2 DM in the Chinese Han population.     

Association of RAGE gene polymorphism with circulating AGEs level and paraoxonase activity in relation to macro-vascular complications in Indian type 2 diabetes mellitus patients

Background and aims

Sustained interaction of advanced glycation end products (AGEs) with their receptor RAGE and subsequent signaling plays an important role in the development of diabetic complications. Genetic variation of RAGE gene may be associated with the development of vascular complications in type 2 diabetes mellitus (T2DM).

Objectives

The present study aimed to explore the possible association of RAGE gene polymorphisms namely − 374T/A, − 429T/C and G82S with serum level of AGEs, paraoxonase (PON1) activity and macro-vascular complications (MVC) in Indian type 2 diabetes mellitus patients (T2DM).

Methods

A total of 265 diabetic patients, including DM without any complications (n = 135), DM-MVC (n = 130) and 171 healthy individuals were enrolled. Genotyping of RAGE variants were assessed by polymerase chain reaction-restriction fragment length polymorphism. Serum AGEs were estimated by ELISA and fluorometrically. and PON1 activity was assessed spectrophotometrically.

Results

Of the three examined SNPs, association of − 429T/C polymorphism with MVC in T2DM was observed (OR = 3.001, p = 0.001) in the dominant model. Allele ‘A’ of − 374T/A polymorphism seems to confer better cardiac outcome in T2DM. Patients carrying C allele (− 429T/C) and S allele (G82S) had significantly higher AGEs levels. − 429T/C polymorphism was also found to be associated with low PON1 activity. Interaction analysis revealed that the risk of development of MVC was higher in T2DM patients carrying both a CC genotype of − 429T/C polymorphism and a higher level of AGEs (OR = 1.343, p = 0.040).

Conclusion

RAGE gene polymorphism has a significant effect on AGEs level and PON1 activity in diabetic subjects compared to healthy individuals. Diabetic patients with a CC genotype of − 429T/C are prone to develop MVC, more so if AGEs levels are high and PON1 activity is low.     

Associations study of vitamin D receptor gene polymorphisms with diabetic microvascular complications: a meta-analysis

Background

Emerging evidence from preclinical and clinical studies has shown that vitamin D plays an important role in the pathogenesis of diabetic microvascular complications (DMI). Several potentially functional polymorphisms (ApaI, BsmI, FokI and TaqI) of vitamin D receptor (VDR) gene have been implicated in DMI risk, but individually published studies showed inconclusive results. The aim of this study was to quantitatively summarize the association between VDR polymorphisms and DMI risk.

Methods

We searched all the publications about the associations mentioned as above from PubMed and ISI database updated in December 2013. Meta-analysis of the overall odds ratios (ORs) with 95% confidence intervals (CIs) was calculated with the fixed or random effect model.

Results

Eight studies involving 2734 subjects were included. Allelic and genotypic comparisons between cases and controls were evaluated. Overall analysis suggests that no significant association was observed among the ApaI, BsmI, FokI and TaqI variants and DMI risk in diabetic patients (all P values > 0.05). In the stratified analysis, significant association was observed with diabetic nephropathy (DN) for VDR gene FokI polymorphism under a dominant model (OR 1.35, 95% CI 1.05–1.74, P = 0.02) in Caucasians.

Conclusions

This meta-analysis indicated that the FokI polymorphism in VDR gene might affect individual susceptibility to DN in Caucasians. Further investigations are needed to confirm our results.     

Variants of NLRP3 gene are associated with insulin resistance in Chinese Han population with type-2 diabetes

Aims

Nod like receptor pyrin domain containing 3 (NLRP3) is the best characterized member of nod like receptor family. Recent studies suggest that NLRP3 plays a crucial role in the pathogenesis of type-2 diabetes (T2DM), and variants in NLRP3 affect its mRNA stability and expression. Therefore, we hypothesize that the variants in NLRP3 gene may contribute to T2DM susceptibility. The aim of this study is to evaluate the association of NLRP3 SNPs with T2DM in Chinese Han patients.

Methods

Two common variants in NLRP3 gene, rs10754558 and rs4612666, were detected using the polymerase chain reaction–restriction fragment length polymorphism procedure in 952 unrelated T2DM patients and 871 healthy controls. All participants were unrelated Chinese Hans.

Results

The GG genotype and G allele frequencies of rs10754558 were significantly higher in T2DM patients than those in controls (for GG genotype, 19.6% vs. 14.5%, p = 0.019; for G allele, 43.9% vs. 39.8%, p = 0.013). The GG genotype of rs10754558 was significantly associated with higher LDL-C levels and more prone to insulin resistance, as evaluated by HOMA-IR or QUICK indexes.

Conclusions

The variant (rs10754558) in NLRP3 is related to insulin resistance and increased risk of T2DM in Chinese Han population.     

Single nucleotide polymorphisms in the mitochondrial control region are associated with metabolic phenotypes and oxidative stress

Objective

To identify the mitochondrial DNA (mtDNA) single nucleotide polymorphisms (SNPs) in the control region and elucidate their role in metabolic phenotypes and oxidative stress.

Methods

A total of 861 nondiabetic subjects were enrolled, including 250 impaired fasting glucose (IFG) and 370 obese subjects (body mass index [BMI] > 25 kg/m²). Antioxidant status presented as total free thiol level was determined from serum samples. DNA was extracted from peripheral blood leucocytes, and the sequences were analyzed using the DNASTAR software. SNPs were identified by comparison with the Cambridge Reference Sequence.

Results

After adjusting odds ratios for age, sex, and BMI, the selected independently significant SNPs indicated 4 susceptible SNPs: SNP-16126C and SNP-16261T, which were related to abdominal obesity (P = 0.009; 0.06); SNP-16390A, related to hypertension (HTN) (P = 0.007); and SNP-16092C, related to decreased antioxidant capacity (P = 0.015). In the obese subgroup, 3 susceptible SNPs included SNP-16189C and SNP-16260T, which showed significantly higher IFG prevalence (P = 0.016 and 0.024, respectively), and SNP-16519C, which was significantly higher in the HTN group (P = 0.036). As to protective SNPs, 5 protective SNPs were identified in all subjects but only one SNP-16093C is consistent in obese group, which showed a significantly lower prevalence in patients with abdominal obesity and was associated with a higher antioxidant status (P < 0.001).

Conclusion

SNPs in the mtDNA control region are associated with metabolic phenotypes and oxidative stress markers. Some SNPs are relating to the interaction between obesity and genetic factors. The beneficial effects of these protective SNPs were insignificant and some susceptible SNPs became dominant within the obese subgroup. Subjects harboring these SNPs should avoid excessive weight gain.     

Association of PARP-1, NF-κB,NF-κBIA and IL-6, IL-1β and TNF-α with Graves Disease and Graves Ophthalmopathy

Background

Graves Disease (GD) is an autoimmune disorder affected by an interaction of multiple genes such as Nuclear Factor-κB (NF-κB), Nuclear Factor-κB Inhibitor (NF-κBIA), Poly (ADP-ribose) polymerase-1 (PARP-1) and cytokines like Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor-α (TNF-α) and mostly accompanied by an ocular disorder, Graves Ophthalmopathy (GO). We hypothesize that there is a relationship between GD, GO, polymorphisms of inflammatory related genes and their association with cytokines, which may play important roles in autoimmune and inflammatory processes.

Subjects and methods

To confirm our hypothesis, we studied the polymorphisms and cytokine levels of 120 patients with GD and GO using PCR-RFLP and ELISA methods, respectively.

Results

We found that patients with GG genotype and carriers of G allele of PARP-1 G1672A polymorphism are at risk in the group having GD (p = 0.0007) while having GA genotype may be protective against the disease. PARP-1 C410T polymorphism was found to be associated with GO by increasing the risk by 1.7 times (p = 0.004). Another risk factor for development of GO was the polymorphism of del/ins of NFkB1 gene (p = 0.032) that increases the risk by 39%. Levels of cytokines were also elevated in patients with GD, but no association was found between levels of cytokines and the development of GO as there was no change in levels of cytokines.

Conclusions

We suggest that, PARP-1 and NFkB1 gene polymorphisms may be risk factors for developing Graves Disease and Ophthalmopathy.     

Association of peroxisome proliferator activated receptor-γ gene with non-alcoholic fatty liver disease in Asian Indians residing in north India

Background

Genetics of non-alcoholic fatty liver (NAFLD) in Asian Indians has been inadequately studied. We investigated the association of polymorphisms C161T and Pro12Ala of peroxisome proliferator-activated receptor gamma (PPARγ) with clinical and biochemical parameters in Asian Indians with NAFLD.

Methods

In this case–control study, 162 NAFLD cases and 173 controls were recruited. Abdominal ultrasound, clinical and biochemical profiles, fasting insulin levels and value of homeostasis model assessment of insulin resistance were determined. Polymerase chain reaction–restriction fragment length polymorphisms of two polymorphisms were performed. The association of these polymorphisms with clinical and biochemical parameters was analysed.

Results

Higher frequency of Ala and T alleles of PPARγ was obtained in cases. Ala/Ala genotype of PPARγ (Pro12Ala) was associated with significantly higher serum triglycerides (TG), alkaline phosphatase (ALK) and waist–hip ratio in cases as compared to controls. In C161T polymorphism, TT genotype was significantly increased TG (p = 0.04), total cholesterol (p = 0.01), ALK (p = 0.04) and gamma-glutamyl transpeptidase (p = 0.007) in cases. The linkage disequilibrium for these two single-nucleotide polymorphisms of PPARγ was differed in cases (D1 = 0.1; p = 0.006) and controls (D1 = 0.07; p = 0.1). Using a multivariate analysis after adjusting for age, sex and body mass index, the presence of NAFLD was linked to these two polymorphisms (odds ratio 1.64 (95% CI: 1.09–2.45, p = 0.05)].

Conclusion

Asian Indians in north India carrying the alleles Ala and T of PPARγ (Pro12Ala and C161T) polymorphisms are predisposed to develop NAFLD.     

Association of glutathione S-transferase M1/T1 polymorphisms with susceptibility to vitiligo

Background

Some studies suggested that Glutathione S-transferases M1/T1(GSTM1/T1) null polymorphisms may be associated with the risk of vitiligo.

Aims

The purpose of this study is to further evaluate the association between GSTM1/T1 null polymorphisms and the susceptibility to vitiligo.

Methods

We carried out a retrieval of studies in the databases. Odds ratios (OR) and 95% confidence intervals (95% CIs) were used to assess the strength of this association. We analyzed the data using Stata 11.0.

Results

Six case–control studies including 1358 cases and 1673 controls were included in this meta-analysis. Our overall results showed the GSTM1 or GSTT1 null polymorphism was associated with vitiligo (GSTM1:OR = 1.59, 95% CI: 1.21–2.08, P = 0.001; GSTT1: OR = 1.30, 95% CI: 1.12–1.51, P = 0.001). In the subgroup analysis, the GSTM1 null polymorphism might be a genetic risk factor to vitiligo in East Asian (OR = 1.71, 95% CI: 1.12–2.63, P = 0.014) but not in the Mediterranean, however individuals with the GSTT1 null polymorphism in the Mediterranean (OR = 1.76, 95% CI: 1.15–2.71, P = 0.010) but not in East Asian have a greater predisposition to vitiligo. In addition there was also a significant trend toward an association with the combination of the GSTM1 null and GSTT1 null in either East Asians or Mediterraneans.

Conclusion

The GSTM1/T1 null polymorphisms may be associated with vitiligo. More studies are needed to confirm this conclusion.     

Polymorphisms of the TLR4 gene and risk of gastric cancer

Objective

Toll-like receptor 4 (TLR4) is an important lipo-polysaccharide (LPS) receptor in gastric epithelial cell signaling transduction and plays critical roles in the development and progression of gastric cancer (GC). We investigated the effects of TLR4 gene polymorphisms and gene–environmental interactions on the risk of GC in Northeastern China.

Methods

We genotyped two single-nucleotide polymorphisms (SNPs) in TLR4 (rs10116253 and rs1927911) in 217 GC patients and 294 cancer-free controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated by unconditional logistic-regression models.

Results

Individuals carrying CC genotype of rs10116253 and TT genotype of rs1927911 had a significantly decreased risk of GC (adjusted OR = 0.33, 95% CI 0.18–0.60, P < 0.001 and adjusted OR = 0.37, 95% CI 0.21–0.67, P = 0.001 respectively), compared with TT genotype of rs10116253 and CC genotype of rs1927911. In addition, the SNP effects were additive to the effects of some known environmental factors without any interaction between them in the susceptibility to GC.

Conclusion

Our data suggested that TLR4 gene polymorphisms may be associated with a decreased risk of GC in Chinese population. And these SNPs and their combined effects with environmental factors may be associated with the risk of GC.     

Utility of large consanguineous family-based model for investigating the genetics of type 2 diabetes mellitus

Objectives

This study examined the utility of a family-based model for replicating the results of genome-wide association studies (GWAS) of type 2 diabetes (T2D).

Methods and results

In a total of 232 members of a large consanguineous Omani Arab pedigree (age: 16–80 years), there were 27 diabetics and 50 prediabetics (17 with impaired fasting glucose and 33 with impaired glucose tolerance). All 232 individuals underwent anthropometric and biochemical investigations and genotyped for 14 known common gene variants of modest effect on T2D risk. Power analysis at a LOD score of 3, gave 80% power to locate a single specific locus that accounts for 52% of the total phenotypic variation. Measured genotype analysis (MGA) was used to determine heritability of various quantitative traits (QTs) which ranged 25–56%. Using MGA, some common gene variants were found to have little (< 5%) but significant impact on the heritability of T2D related QTs [KCNJ11 (rs5219), p = 0.004]; [IGF2BP2 (rs4402960), p = 0.02]; [SLC30A8 (rs13266634), p = 0.05]; [CAPN10 (rs2975760), p = 0.031]; [FTO (rs8050136), p = 0.023]; [FTO (rs9939609), p = 0.018] and [SLC30A8 (rs13266634), p = 0.05]. Sib-TDT analysis showed that some gene variants were significantly associated with T2D risk but didn't reach the level of significance after Bonferroni correction [KCNJ11 (rs5219), p = 0.047] and [CAPN10 (rs41266971), p = 0.035].

Conclusion

We have demonstrated that, in principle, a family-based model with minor limitations could be used to replicate some of the results of large GWAS case–control studies. This model could successfully be applied for the future discovery, by deep sequencing, of rare gene variants.     

Cyclooxygenase-2 169C > G and 8473T > C gene polymorphisms and prostaglandin E2 level in breast cancer: A case–control study

Aims

Cyclooxygenase 2 (COX-2) with the resulting prostaglandin E2 (PGE2) is linked to increased risk of human breast cancer (BC). The aim of this study was to determine COX-2 169C > G and 8473T > C gene polymorphisms and PGE2 level at various stages of BC clarifying the role of COX-2 gene polymorphism and PGE2 in relation to BC.

Methods

The study population comprised 160 women at different stages of BC and 150 gender- and age-matched healthy control subjects. Plasma PGE2 was measured by ELISA, the COX-2 gene polymorphisms were determined using PCR-RFLP.

Results

The variant alleles COX-2 169G and 8473C were significantly associated with BC susceptibility [OR = 3.1, 95% CI (2.2–4.4), P < 0.001 for 169C>G and OR = 1.74, 95%CI (1.3–2.4), P = 0.005 for 8473C]. However, both COX-2 gene polymorphisms were not associated with breast cancer stage. Plasma PGE2 levels were significantly increased in patients compared to the controls. In early and late stages of BC, there was a significant increase in the plasma PGE2 levels towards the presence of homozygous GG compared with homozygous CC (P < 0.001) for 169 C>G, also towards the presence of CC than TT (P < 0.001) for 8473T>C SNP.

Conclusion

The 169C>G and 8473T>C polymorphisms of the COX-2 gene were associated with the BC in Egyptian women. Furthermore, individuals with COX-2 169GG and 8473CC genotypes showed significant increase in plasma PGE2 levels. PGE2 levels may serve as a predictor of poor prognosis in patients with BC.     

Vitamin D status and vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Egyptian children

Background

Type 1 diabetes mellitus (T1DM) is recognized as a T-cell-mediated autoimmune disease. Vitamin D compounds are known to suppress T-cell activation by binding to vitamin D receptor (VDR); and thus, VDR gene polymorphisms may be related to T-cell-mediated autoimmune diseases. The aim of this study was to investigate the association between vitamin D status and VDR gene polymorphisms and T1DM.

Materials and methods

One hundred and twenty patients with T1DM and one hundred and twenty controls were enrolled in the study. VDR gene BsmI, FokI, ApaI and TaqI polymorphisms were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum 25-hydroxyvitamin D (25(OH)D) was determined using ELISA.

Result

Serum 25(OH)D levels revealed a vitamin D deficiency or insufficiency in 75% of the patients. The mean levels of vitamin D were significantly lower in patients as compared to their controls (P = < 0.001). VDR BsmI Bb and bb genotypes and VDR FokI Ff and ff genotypes were associated with increased risk of T1DM (OR = 2.3, 95% CI = 1.3–4.2, P = 0.005; OR = 2.2, 95% CI = 1.1–4.7, P = 0.04; OR = 1.8, 95% CI = 1.03–3.04, P = 0.04; OR = 4.03, 95% CI = 1.2–13.1, P = 0.01 respectively), while the VDR ApaI and TaqI polymorphisms were not.

Conclusion

Our study indicated that vitamin D deficiency and VDR BsmI and FokI polymorphisms were associated with T1DM in Egyptian children.     

A polymorphism of matrix Gla protein gene is associated with kidney stone in the Chinese Han population

Purpose

Matrix Gla protein (MGP) is a molecular determinant regulating the extracellular matrix calcification. To further confirm whether the MGP genetic polymorphism was universally associated with the risk of kidney stone, we investigated the association of genetic polymorphisms of MGP with kidney stone in the Chinese Han population.

Materials and methods

728 subjects were recruited for the study. We firstly re-sequenced the human genomic MGP gene including the 1500 bp promoter, 5′-UTR, 4 exons and 3′-untranslated regions, identified single nucleotide polymorphisms (SNPs) in MGP, and performed an association analysis with kidney stones in 54 subjects of the Chinese Han population. A candidate tag SNP was genotyped in total subjects using an allele specific PCR, and further analyzed the association with kidney stone.

Results

We identified 18 polymorphisms including four tag SNPs. A tag SNPrs4236 was associated with kidney stones. The G allele carrier had a 1.373-fold reduced kidney stone risk compared with A allele carriers in SNPrs4236 (odds ratios (OR) = 1.373; 95%CI, 1.051–1.793; p = 0.019). However, we did not find an association between the polymorphism and clinical characteristics of kidney stones.

Conclusions

Our findings showed that SNPrs4236 of the MGP gene is associated with kidney stones in the Chinese Han population, and influences the genetic susceptibility to kidney stones. In the future, functional assays of the polymorphism should permit a better understanding of the role of MGP genetic variants and kidney stones.     

Meta-analyses of HFE variants in coronary heart disease

Aim

HFE gene variants can cause hereditary hemochromatosis (HH) that often comes along with an increased risk of coronary heart disease (CHD). The goal of our study is to assess the contribution of four HFE gene variants to the risk of CHD.

Methods and results

We conducted four meta-analyses of the studies examining the association between four HFE gene variants and the risk of CHD. A systematic search was conducted using MEDLINE, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI), Wanfang Chinese Periodical.

Results

Meta-analyses showed that HFE rs1799945-G allele was associated with a 6% increased risk of CHD (P = 0.02, odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.01–1.11). However, no association between the other three HFE gene variants (rs1800562, rs1800730, and rs9366637) and CHD risk was observed by the meta-analyses (all P values > 0.05). In addition, the results of our case–control study indicated that rs1800562 and rs1800730 were monomorphic, and that rs1799945 and rs9366637 were not associated with CHD in Han Chinese.

Conclusions

Our meta-analysis suggested that a significant association existed between rs1799945 mutation and CHD, although this mutation was rare in Han Chinese.