Associations of rs3740677 within <Emphasis Type="Italic">GAB2</Emphasis> Gene with LOAD in Chinese Han Population

GRB2-associated binding protein 2 (GAB2) has been identified as a crucial factor in Alzheimer’s disease (AD), and ten common variants within GAB2 have been detected to be associated with AD onset risk in genome-wide association studies (GWAS). Here, we first screened a common locus (rs3740677) in 3′ UTR of GAB2 sequence which is targeted by the miRNA-185 and initiatively explored the probable associations of rs3740677 with risk for late-onset AD (LOAD) in a large scale case–control study from Chinese Han populations (992 LOAD patients and 1358 healthy subjects). Eventually, the genotype (P?=?0.024) and allele (P?=?0.008) distribution of rs3740677 showed significant difference between LOAD and control group, and we observed a significant association of T allele in rs3740677 with LOAD risk in multivariate analysis and it decreased the risk for LOAD (dominant: OR?=?0.831, 95 % CI?=?0.702–0.983, P?=?0.031; additive: OR?=?0.855, 95 % CI?=?0.745–0.983, P?=?0.027) adjusted for age, gender, and APOE ε4 status. Our study further confirmed the association of GAB2 and AD. However, the absolute and correct association of rs3740677 with AD still required more investigations in diverse regions and ethnics.     

SORL1 Is Associated with the Risk of Late-Onset Alzheimer’s Disease: a Replication Study and Meta-Analyses

The sorting-related receptor gene (SORL1) has been defined as an interesting candidate gene for Alzheimer’s disease (AD). Recently, one novel variant, rs11218343, within SORL1 was reported to be related to late-onset Alzheimer’s disease (LOAD) in Caucasians, Korean, and Japanese. The aim of this case–control study is to investigate whether SORL1 rs11218343 contributes to susceptibility for LOAD in Chinese. Furthermore, our data, along with previously studies, were pooled for determining the risk of the rs11218343 polymorphism on LOAD. The rs11218343 polymorphism was genotyped in the 2350 independent subjects from Northern Han Chinese population (including 992 cases and 1358 age- and gender-matched controls). Result of the case–control study showed the association between rs11218343 polymorphism and the risk of LOAD in a Northern Han Chinese population (recessive model: odds ratio (OR)?=?0.641, 95 % confidence interval (CI)?=?0.464–0.884, P?=?0.007; additive model: OR?=?0.873, 95 % CI?=?0.765–0.996, P?=?0.043). The results of meta-analysis in subgroups (Caucasian and Asian) and the whole showed that the minor allele (C allele) within rs11218343 played a protective effect on AD risk (OR (95 % CI), 0.77 (0.72–0.83), 0.85 (0.79–0.91), 0.81 (0.76–0.85), respectively). In conclusion, the C allele in SORL1 rs11218343 may be a protective factor for LOAD in both Caucasian and Han Chinese.     

Maternal <Emphasis Type="Italic">MTHFR</Emphasis> polymorphism (677 C–T) and risk of Down’s syndrome child: meta-analysis

Methylenetetrahydrofolate reductase (MTHFR) is the most important gene that participates in folate metabolism. Presence of valine instead of alanine at position 677 and elevated levels of homocystein causes DNA hypomethylation which in turn favours nondisjunction. In this study, we conducted a meta-analysis to establish link between maternal single-nucleotide polymorphism (SNP) and birth of Down’s syndrome (DS) child. A total of 37 case–control studies were selected for analysis including our own, in which we investigated 110 cases and 111 control mothers. Overall, the result of meta-analysis showed significant risk of DS affected by the presence of maternal SNP (MTHFR 677 C–T OR = 0.816, 95% CI = 0.741–0.900, P<0.0001). Heterogeneity of high magnitude was observed among the studies. The chi-square value suggested a highly significant association between homozygous mutant TT genotype and birth of DS child (χ²=23.63, P=0.000). Genetic models suggested that ‘T’ allele possesses high risk for DS whether present in dominant (OR = 1.23, 95% CI = 1.13–1.34); codominant (OR = 1.17, 95% CI = 1.10–1.25) or recessive (OR = 1.21, 95% CI = 1.05–1.38) form. The analysis from all 37 studies combined together suggested that MTHFR 677 C–T is a major risk factor for DS birth.     

The relationship between human leukocyte antigen-DP/DQ gene polymorphisms and the outcomes of HCV infection in a Chinese population

Background

Recently, human leukocyte antigen (HLA) class-II gene polymorphisms have been reported to be related to Hepatitis C virus (HCV) infection and chronicity. The objective of this study was to explore the relationship of HLA-DP rs9277535 and HLA-DQ rs7453920 with the outcomes of HCV infection.

Methods

The rs9277535 and rs7453920 were genotyped in 370 subjects with chronic HCV infection, 194 subjects with spontaneous HCV clearance, and 973 subjects with non-HCV infection from the Chinese population using the ABI TaqMan allelic discrimination assay.

Results

Logistic regression analyses showed that the minor allele A of rs7453920 significantly increased the susceptibility of HCV infection in dominant model (adjusted OR?=?1.33, 95% CI: 1.04–1.71, P?=?0.026) and additive models (adjusted OR?=?1.30, 95% CI: 1.06–1.60, P?=?0.012). Rs9277535 A allele significantly increased the risk of chronic HCV infection in dominant model (adjusted OR?=?1.52, 95% CI: 1.01–2.28, P?=?0.046). Haplotype AA showed a higher risk of HCV infection than the most frequent haplotype GG (adjusted OR?=?1.37, 95% CI: 1.05–1.78, P?=?0.018).

Conclusion

The HLA-DQ rs7453920 and -DP rs9277535 mutations were significantly associated with HCV infection susceptibility and chronicity, respectively.

     

Oxidative Stress-Related Genes in Type 2 Diabetes: Association Analysis and Their Clinical Impact

Worldwide prevalence of diabetes mellitus motivates a number of association studies to be conducted throughout the world. Eleven polymorphisms from nine candidate genes in oxidative stress pathway have been analyzed in eastern Indian type 2 diabetic patients (n = 145) and healthy controls (n = 100). Different biochemical parameters were also analyzed for their association with the disease. Significant associations were observed for rs2070424 A>G SOD1 (OR 3.91, 95% CI 2.265–8.142, P < 0.001), rs854573 A>G PON1 (OR 3.415, 95% CI 2.116–5.512, P < 0.001), rs6954345 G>C PON2 (OR 3.208, 95% CI 2.071–4.969, P < 0.001), RAGE rs1800624 ?374 T>A (OR 3.58, 95% CI 2.218–5.766, P < 0.001), and NOS3 ?786 T>C (OR 3.75, 95% CI 2.225–6.666, P < 0.001). Haplotype containing two risk alleles of PON1 and PON2 genes was significantly associated with disease (OR 8.34, 95% CI 1.554–44.804, P < 0.002). Our results suggest that carriers of major and efficient alleles of oxidative stress genes are more likely to survive the comorbid complications and single copy of risk allele is sufficient for developing the disease.     

Association of <Emphasis Type="Italic">FGFR2</Emphasis> (rs2981579) gene polymorphism with the risk of mesial occlusion

The molecular-genetic testing of the polymorphic rs2981579 (C>T) locus of the FGFR2 gene as the marker of increased predisposition to the development of mesial occlusion was carried out in 110 patients with mesial occlusion and 103 general-population control subjects from Ukraine. It was shown that polymorphism rs2981579 in gene FGFR2 is associated with mesial occlusion (OR = 1.67, 95% CI = 1.14–2.45, p = 0.009). Compared to CC carriers, TT+CT carriers had a 3.21-fold higher risk of mesial occlusion (95% CI = 1.57–6.57, p = 0.001). We found the protective effect of the homozygous allele C on mesial occlusion development (OR = 0.31, p = 0.001). This is the first published data on FGFR2 polymorphisms rs2981579 (C>T) in patients with mesial occlusion.     

LncRNA <Emphasis Type="Italic">ANRIL</Emphasis> Expression and <Emphasis Type="Italic">ANRIL</Emphasis> Gene Polymorphisms Contribute to the Risk of Ischemic Stroke in the Chinese Han Population

The aim of the present study was to explore the role of lncRNA ANRIL in the pathogenesis of ischemic stroke (IS) and coronary artery disease (CAD) and to determine the association between ANRIL variants and the genetic susceptibility of IS and CAD in the Chinese Han population. A genetic association study including 550 IS patients, 550 CAD patients, and 550 healthy controls was conducted. The expression levels of lncRNA ANRIL, CDKN2A, and CDKN2B were detected using qRT-PCR. Genotyping was performed by Sequenom MassARRAY on an Agena platform. Our study showed that IS patients had an increased lncRNA ANRIL expression (P?=?0.002) and a decreased CDKN2A expression (P?<?0.001) compared with normal controls. A significant difference with regard to the genotype distribution of rs2383207 was found between male IS patients and controls (P?=?0.011). The minor allele of rs2383207 significantly increased the IS risk under a recessive model (OR?=?1.52, 95% CI?=?1.05–2.21, P?=?0.027). The minor allele of rs1333049 was significantly associated with the risk of IS among the male patients under a recessive model (OR?=?1.56, 95% CI?=?1.04–2.35, P?=?0.031). However, no significant association was found between the ANRIL variants and the risk of CAD (all P?>?0.050). In addition, we found a decreased lncRNA ANRIL expression in IS patients who carried the GG genotype of rs1333049 compared with IS patients who carried the CC or CG genotype (P?=?0.041). In summary, we found that IS patients had an increased lncRNA ANRIL expression and a decreased CDKN2A expression compared with the controls, which might play an impellent role in pathological processes of IS. The ANRIL variants rs2383207 and rs1333049 were significantly associated with the risk of IS among males but not females in the Chinese Han population.     

A Missense Variant in <Emphasis Type="Italic">TREML2</Emphasis> Reduces Risk of Alzheimer’s Disease in a Han Chinese Population

Recently, Benitez and colleagues re-analyzed whole-exome sequencing data and revealed that a coding missense variant (rs3747742-C) in triggering receptor expressed on myeloid cells-like 2 (TREML2) gene reduced late-onset Alzheimer’s disease (LOAD) risk in Caucasians. To date, no study was carried out to test this association in other ethnic groups and populations, including Han Chinese. Therefore, the aim of the current study was to validate the relation between rs3747742 and LOAD susceptibility in a large Han Chinese population including 992 LOAD patients and 1358 healthy controls. In the total sample, the minor (C) allele of rs3747742 was associated with a reduced LOAD risk under the recessive genetic model after Bonferroni correction (odds ratio (OR)?=?0.713; 95 % confidence interval (CI): 0.546–0.932; P?=?0.013, Bonferroni-corrected P?=?0.039). Interestingly, after stratifying data according to apolipoprotein E (APOE) ε4 status, we revealed that this protection only exists in APOE ε4 carriers (recessive genetic model, OR?=?0.448; 95 % CI: 0.262–0.765; P?=?0.003, Bonferroni-corrected P?=?0.009) in our cohort. Taken together, our findings support rs3747742-C as a protective factor for LOAD, especially in APOE ε4 carriers.     

Association of polymorphic markers of chemokine genes,their receptors,and <Emphasis Type="Italic">CD14</Emphasis> gene with coronary atherosclerosis

Atherosclerosis represents an inflammatory response to the disturbance of the endothelial layer in the arterial bloodstream. In the present study, an analysis of associations of polymorphic markers for the genes controlling synthesis of proteins involved in atherosclerosis pathogenesis in coronary atherosclerosis (CA) patients (217 subjects) and in a control group (250 subjects) was conducted. The following genes were examined: rs991804 (CCL2 gene), rs1126579 (CXCR2 gene), rs4074 (CXCL1 gene), rs4073 (CXCL8 gene), rs333 (CCR5 gene), rs2471859 (CXCR4 gene), rs1801157 (CXCL12 gene), and rs2569190 (CD14 gene). Using the Monte Carlo and Markov chain (APSampler) method, allele/genotype combinations associated with both low and high CA risk were revealed. The most important findings included the following: CXCR4*T/T + CCL2*C + CCR5*I/I (P_perm = 1 × 10^–6, OR = 0.44, 95% CI 0.3–0.63), CXCR2*C + CD14*C + CXCL12*G + CCL2*C + CCR5*D (P_perm = 4 × 10^–6, OR = 5.78, 95% CI 2.34–14.28), CD14*C + CCL2*C/C + CCR5*D (P_perm = 6.3 × 10^–6, OR = 5.81, 95% CI 2.17–15.56), CXCL8*A + CXCR2*C + CD14*T + CXCR4*C (P_perm = 0.01, OR = 3.21, 95% CI 1.63–6.31).     

Association between <Emphasis Type="Italic">ATM</Emphasis> gene polymorphisms,lung cancer susceptibility and radiation-induced pneumonitis: a meta-analysis

Background

Previous studies have suggested that DNA double-strand break (DSB) repair is an important protective pathway after damage. The ataxia telangiectasia mutated (ATM) gene plays an important role in the DNA DSB repair pathway. DNA damage is a major cytotoxic effect that can be caused by radiation, and the ability to repair DNA after damage varies among different tissues. Impaired DNA repair pathways are associated with high sensitivity to radiation exposure. Hence, ATM gene polymorphisms are thought to influence the risk of cancer and radiation-induced pneumonitis (RP) risk in cancer patients treated with radiotherapy. However, the results of previous studies are inconsistent. We therefore conducted this comprehensive meta-analysis.

Methods

A systematic literature search was performed in the PubMed, Embase, China National Knowledge Internet (CNKI) and Wanfang databases to identify studies that investigated the association between the ATM gene polymorphisms and both lung cancer and RP radiotherapy-treated lung cancer (the last search was conducted on Dec.10, 2015). The odds ratio (OR) and 95% confidence interval (CI) were used to investigate the strength of these relationships. Funnel plots and Begg’s and Egger’s tests were conducted to assess the publication bias. All analyses were performed in STATA 13.0 software.

Results

Ten eligible case-control studies (4731 cases and 5142 controls) on lung cancer susceptibility and four (192 cases and 772 controls) on RP risk were included. The results of the overall and subgroup analyses indicated that in the ATM gene, the rs189037 (?111G?>?A, ?4519G?>?A), rs664677 (44831C?>?T, 49238C?>?T) and rs664143 (131,717 T?>?G) polymorphisms were significantly associated with lung cancer susceptibility (OR?=?1.21, 95% CI?=?1.04–1.39, P?=?0.01; OR?=?1.26, 95% CI?=?1.06–1.49, P?=?0.01; OR?=?1.43, 95% CI?=?1.15–1.78, P?<?0.01). Additionally, the rs189037 variant was significantly associated with RP risk (OR?=?1.74, 95% CI?=?1.02–2.97, P?=?0.04). No publication bias was found in the funnel plots, Begg’s tests or Egger’s tests.

Conclusions

The results indicate that the ATM rs189037, rs664677 and rs664143 gene polymorphisms are risk factors for lung cancer, while the ATM rs189037 variant was significantly associated with RP risk.

     

Polymorphism in promoter regions of matrix metalloproteinases (<Emphasis Type="Italic">MMP1</Emphasis>, <Emphasis Type="Italic">MMP9</Emphasis>, and <Emphasis Type="Italic">MMP12</Emphasis>) in chronic obstructive pulmonary disease patients

Our studies have shown that the genotype and allele frequencies of polymorphisms G(?1607)GG of MMP1 gene, C(?1562)T of MMP9 gene, and A(?82)G of MMP12 gene do not significantly differ in the samples of chronic obstructive pulmonary disease (COPD) patients (N = 318) and healthy controls (N = 319) dwelling in Bashkortostan Republic. However, association of (?1562)T allele of the MMP9 gene with the severity of COPD disease progression has been revealed. In COPD patients at stage 4 of the disease, the frequency of allele T was significantly higher that in patients with the stages 2 and 3 (15.89% versus 8.38%; χ² = 7.804; d.f. = 1; P = 0.005; OR = 2.06 95% CI 1.22–3.49). The distribution of the genotype frequencies of C(?1562)T polymorphism of MMP9 gene significantly differed between the patients with various COPD severity (χ² = 9.849; d.f. = 2; P = 0.007). The individuals with rare genotype TT were revealed only among patients with severe COPD form (3.97% versus 0%; χ² = 4.78; P = 0.029; P _cor = 0.058). Analysis of this polymorphism in patients with early COPD onset (younger than 55 years old) has shown a significant increase in the allele T frequency in the group of patients with severe COPD (stage 4 according to GOLD) compared to the patients of the same age but with less severe COPD progression (χ² = 5.26; d.f. = 1; P = 0.022). As the major clinical characteristics of stage 4 COPD is the development of pulmonary emphysema as well as bronchial walls deformation, we suggest that the increased expression of MMP9 gene caused by genetic polymorphism in the gene promoter is important in the early development of serious complications of the disease.     

Polymorphisms in the 3′-UTR of <Emphasis Type="Italic">SCD5</Emphasis> gene are associated with hepatocellular carcinoma in Korean population

The purpose of the study was to assess the relationship between polymorphisms of the SCD5 and MMP1 gene and hepatocellular carcinoma (HCC). The gene polymorphisms with a minor allele frequency (MAF)?>?0.05 were selected eight SNPs (rs6840, rs1065403, rs3821974, and rs3733230 in 3?-UTR; rs4693472, rs3733227, rs1848067, and rs6535374 in intron region) of SCD5 gene and two SNPs (rs1799750 and rs1144393 in promoter region) of MMP1 gene. The genotype of SCD5 and MMP1 gene SNPs were determined by direct sequencing and pyrosequencing, respectively. One hundred sixty-two patients with HCC and two hundred twenty-five control subjects were recruited in Korean male population. In terms of genotype frequencies, SCD5 genotype TC, GA, AG, and CG of rs6840, rs1065403, rs3821974, and rs3733230, respectively were higher in control group than HCC. In addition, these genotype decreased the risk (rs6840; OR 0.55, 95% CI 0.31–0.99; rs1065403; OR 0.46, 95% CI 0.26–0.83; rs3821974; OR 0.56, 95% CI 0.31–0.99; rs3733230; OR 0.62, 95% CI 0.34–1.12) of HCC, which may work as a prevention of HCC. At least one minor allele carrier of SCD5 gene polymorphisms were related to decreased risk of HCC for AFP cut-point levels >?200 or >?400 ng/ml, respectively. Our results indicate that polymorphisms in the 3?-UTR of the SCD5 gene may associated with HCC in the Korean male population.     

Genetic polymorphisms of <Emphasis Type="Italic">T-1131C APOA5</Emphasis> and <Emphasis Type="Italic">ALOX5AP SG13S114</Emphasis> with the susceptibility of ischaemic stroke in Morocco

Ischaemic stroke is a multifactorial disease. Genetic polymorphisms involved in lipid, inflammatory and thrombotic metabolisms play an important role in the development of ischaemic stroke. The present study aimed to assess the relationship between T1131C APOA5 and SG13S114 ALOX5AP polymorphisms and the risk of ischemic stroke in 175 cases and 201 controls. Genotyping was performed by high resolution melting and polymerase chain reaction restriction fragment length polymorphism methods. In the case of T-1131C APOA5, a modest risk of ischaemic stroke was noticed with CC (OR: 2.86; 95% CI = 1.24–6.58; Pc = 0.039) and C allele (OR: 1.54; 95% CI = 1.01–2.33; Pc = 0.014). For SG13S114ALOX5AP, a significant association was observed among subjects with TT (OR: 2.57; 95% CI =1.49–4.83; Pc = 0.009) and T allele (OR: 1.59; 95% CI = 1.16–2.19; Pc = 0.008). According to the risk factors of ischaemic stroke, a positive correlation was observed only between SG13S114 variant of ALOX5AP gene and hypertension (Pc = 0.026). Despite lower sample size, T-1131C APOA5 and SG13S114 variants could be considered an independent genetic risk factor of ischaemic stroke in Moroccan population.     

Associations of polymorphisms in the candidate genes for Alzheimer’s disease <Emphasis Type="Italic">BIN1, CLU,CR1</Emphasis> and <Emphasis Type="Italic">PICALM</Emphasis> with gestational diabetes and impaired glucose tolerance

Alzheimer’s disease (AD) is the most common type of dementia, with a prevalence that is rising every year. AD is associated with type 2 diabetes mellitus (T2DM) and insulin resistance, and is therefore sometimes called “type 3 diabetes mellitus”. The aim of this study was to examine whether the variants of some candidate genes involved in the development of AD, namely BIN1 (rs744373), CLU (rs11136000), CR1 (rs3818361), and PICALM (rs3851179), are related to several disorders of glucose metabolism—gestational diabetes (GDM), T2DM and impaired glucose tolerance (IGT). Our study included 550 women with former GDM and 717 control women, 392 patients with T2DM and 180 non-diabetic controls, and 117 patients with IGT and 630 controls with normal glucose tolerance. Genotyping analysis was performed using specially-designed TaqMan assays. No significant associations of the genetic variants rs744373 in BIN1, rs11136000 in CLU, or rs3818361 in CR1 were found with GDM, T2DM or IGT, but rs3851179 in PICALM was associated with an increased risk of GDM. The frequency of the AD risk-associated C allele was significantly higher in the GDM group compared to controls: OR 1.21; 95% CI (1.03–1.44). This finding was not apparent in T2DM and IGT; conversely, the C allele of the PICALM SNP was protective for IGT: OR 0.67; 95% CI (0.51–0.89). This study demonstrates an association between PICALM rs3851179 and GDM as well as IGT. However, elucidation of the possible role of this gene in the pathogenesis of GDM requires further independent studies.     

Bayesian logistic regression in detection of gene–steroid interaction for cancer at <Emphasis Type="Italic">PDLIM5</Emphasis> locus

The PDZ and LIM domain 5 (PDLIM5) gene may play a role in cancer, bipolar disorder, major depression, alcohol dependence and schizophrenia; however, little is known about the interaction effect of steroid and PDLIM5 gene on cancer. This study examined 47 single-nucleotide polymorphisms (SNPs) within the PDLIM5 gene in the Marshfield sample with 716 cancer patients (any diagnosed cancer, excluding minor skin cancer) and 2848 noncancer controls. Multiple logistic regression model in PLINK software was used to examine the association of each SNP with cancer. Bayesian logistic regression in PROC GENMOD in SAS statistical software, ver. 9.4 was used to detect gene–steroid interactions influencing cancer. Single marker analysis using PLINK identified 12 SNPs associated with cancer (P < 0.05); especially, SNP rs6532496 revealed the strongest association with cancer (P = 6.84 × 10^?3); while the next best signal was rs951613 (P = 7.46 × 10^?3). Classic logistic regression in PROC GENMOD showed that both rs6532496 and rs951613 revealed strong gene–steroid interaction effects (OR = 2.18, 95% CI = 1.31?3.63 with P = 2.9 × 10^?3 for rs6532496 and OR = 2.07, 95% CI = 1.24 ?3.45 with P = 5.43 × 10^?3 for rs951613, respectively). Results from Bayesian logistic regression showed stronger interaction effects (OR = 2.26, 95% CI = 1.2 ?3.38 for rs6532496 and OR = 2.14, 95% CI = 1.14 ?3.2 for rs951613, respectively). All the 12 SNPs associated with cancer revealed significant gene–steroid interaction effects (P < 0.05); whereas 13 SNPs showed gene–steroid interaction effects without main effect on cancer. SNP rs4634230 revealed the strongest gene–steroid interaction effect (OR = 2.49, 95% CI = 1.5 ?4.13 with P = 4.0 × 10^?4 based on the classic logistic regression and OR = 2.59, 95% CI = 1.4 ?3.97 from Bayesian logistic regression; respectively). This study provides evidence of common genetic variants within the PDLIM5 gene and interactions between PLDIM5 gene polymorphisms and steroid use influencing cancer.     

Polymorphic variants of glutamate receptor (<Emphasis Type="Italic">GRIK5</Emphasis>, <Emphasis Type="Italic">GRIN2B</Emphasis>) and serotonin receptor (<Emphasis Type="Italic">HTR2A</Emphasis>) genes are associated with chronic

Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease of the respiratory system that affects primarily distal respiratory pathways and lung parenchyma. Smoking tobacco is a major risk factor for COPD. The relationship of HTR4 (rs3995090), HTR2A (rs6313), GRIK5 (rs8099939), GRIN2B (rs2268132), and CHRNB4 (rs1948) gene polymorphisms and COPD, as well as the contribution of these polymorphisms to the variations in quantitative characteristics that describe respiratory function, smoking behavior, and nicotine dependence was assessed in an ethnically homogeneous Tatar population. The polymorphisms of HTR2A (rs6313) (P = 0.026, OR = 1.42 for the CC genotype) and GRIN2B (rs2268132) (P = 0.0001, OR = 2.39 for the TT genotype) were significantly associated with increased risk of COPD. The AA genotype of GRIK5 (rs8099939) had a protective effect (P = 0.02, OR = 0.61). Importantly, the HTR2A (rs6313), GRIN2B (rs2268132), and GRIK5 (rs8099939) polymorphisms were only associated with COPD in smokers. Smoking index (pack-years) was significantly higher in carriers of the GRIK5 genotype AC (rs8099939) (P = 0.0027). The TT genotype of GRIN2B (rs2268132) was associated with COPD in subjects with high nicotine dependence according to the Fagerström test (P = 0.002, OR = 2.98). The TT genotype of HTR2A (rs6313) was associated with a reduced risk of the disease in the group with moderate nicotine dependence (P = 0.02, OR = 0.22). The CC genotype of HTR2A (rs6313) and the TT genotype of GRIN2B (rs2268132) were associated with higher levels of nicotine dependence according to the Fagerström test (P = 0.0011 and P = 0.037). Our results may provide insight into potential molecular mechanisms that involve the glutamate (GRIK5, GRIN2B) and serotonin (HTR2A) receptor genes in the pathogenesis of COPD.     

Effects of <Emphasis Type="Italic">ADIPOQ</Emphasis> polymorphisms on PCOS risk: a meta-analysis

Background

Whether adiponectin (ADIPOQ) polymorphisms are associated with the risk of polycystic ovary syndrome (PCOS) remain controversial. Therefore, we performed this study to better explore correlations between ADIPOQ polymorphisms and PCOS risk.

Methods

Literature retrieve was conducted in PubMed, Medline and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

Results

Eighteen studies were enrolled for analyses. Pooled overall analyses showed that rs1501299 polymorphism was significantly associated with PCOS risk (recessive model: p?=?0.02, OR?=?0.77, 95%CI 0.62–0.95; allele model: p?=?0.001, OR?=?1.15, 95%CI 1.06–1.26). Further subgroup analyses according to ethnicity of participants revealed that rs1501299 and rs2241766 polymorphisms were both significantly correlated with PCOS risk in Caucasians. In addition, rs1501299 polymorphism was also significantly correlated with PCOS risk in East Asians.

Conclusions

Our findings indicated that rs1501299 and rs2241766 polymorphisms might serve as genetic biomarkers of PCOS in certain ethnicities.

     

<Emphasis Type="Italic">A MCP</Emphasis>-<Emphasis Type="Italic">1</Emphasis> promoter polymorphism at G-2518A is associated with spontaneous preterm birth

Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine involved in the pathogenesis of spontaneous preterm birth (SPTB). We examined whether the MCP-1 G-2518A polymorphism is associated with the risk of SPTB in a Chinese population. The MCP-1 G-2518A polymorphism was genotyped in 569 preterm singleton neonates and in 673 term neonates using polymerase chain reaction–restriction fragment length polymorphism analysis. The distribution of the MCP-1 G-2518A genotype and the allele frequencies between the SPTB patients and the controls were not significantly different in the overall sample. However, we found that the AA genotype was associated with significantly increased susceptibility to very SPTB (<32 weeks) [odds ratio (OR) 2.07; 95 % confidence interval (CI), 1.27–3.36; P = 0.005) and extremely SPTB (<28 weeks) (OR 2.74; 95 % CI, 1.10–6.72; P = 0.014) compared with ?2518G-positive genotypes (GG + GA genotypes). When extremely preterm neonates and very preterm neonates were combined, the AA genotype was also significantly associated with increased susceptibility to SPTB (OR 2.23; 95 % CI, 1.40–3.54; P < 0.001). The MCP-1 G-2518A polymorphism was not associated with increased susceptibility to SPTB in patients with premature rupture of the membranes (PROM) or in those without PROM. Our findings suggest that the MCP-1 G-2518A polymorphism may plays a role in mediating the susceptibility to SPTB in the Chinese population. Knowledge of genetic factors contributing to the pathogenesis of SPTB may have implications for screening and treatment of this disorder.     

Association of interleukin-10 (A1082G) gene polymorphism with oral squamous cell carcinoma in north Indian population

The functional polymorphism A1082G in the gene (IL10) for interleukin-10 associated with risk of oral squamous cell carcinoma (OSCC). The present case–control study was to evaluate the possible association between IL10 A1082G gene and OSCC in north Indian population. Analysis of IL10 A1082G genotype in 232 OSCC cases and 221 healthy controls of comparable age, gender, smokers, tobacco chewing and alcohol consumption. IL10 A1082G status in cases and controls were evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The frequencies of IL10 A1082G polymorphism AA, AG, GG genotypes were 29.74, 68.10 and 2.15% in OSCC cases and 57.46, 42.08 and 0.45% in healthy controls. The average frequency of G mutant allele was 36.20% in OSCC cases compared with 21.50% among the controls and this allele was associated with increased risk for OSCC cases. Heterozygous AG genotype was found statistically significant in OSCC cases than in controls (OR = 1.6, 95% CI = 1.1–2.2, P = 0.003), whereas homozygous mutant GG genotype was not found significant (OR = 4.7, 95% CI = 0.55–41.1, P = 0.2). Moreover, we found that G allele was significant in OSCC cases of tobacco chewing. The frequency of IL10 A1082G polymorphism G allele and AG genotype is associated with OSCC cases as compared with controls; this may be due to smoking and tobacco chewing. Our findings showed that in IL10 A1082G gene polymorphism AG genotype and G allele may participate in the progression of OSCC.