Higher Frequency Of AA Genotype Research Articles

Association between primary osteoarthritis and ADAMTS14 single nucleotide polymorphism in Egyptian population: a case-control study

BackgroundPrimary osteoarthritis is considered one of the most common and the most studied musculoskeletal disorder. Nevertheless, the risk factors remain unclear. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 14 (ADAMTS14) gene is involved in the cleavage of amino-terminal propeptides from type II procollagen, a necessary step in the formation of collagen fibers. The abnormal metabolism of collagen fibers type II leads to a decreased mechanical strength of joint cartilage which is one of the most important contributing factors to joint osteoarthritis. We aimed at investigating the association between primary osteoarthritis and ADAMTS14 gene rs4747096 single nucleotide polymorphism in a sample of Egyptian patients and analyzing the relationship between this genetic polymorphism with the severity of osteoarthritis. Sixty-five Egyptian patients who fulfilled the American College of Rheumatology criteria for primary knee osteoarthritis were compared with thirty-one apparently healthy subjects. Genotyping was performed by TaqMan single nucleotide polymorphism genotyping assay.ResultsThere was a statistically significantly higher frequency of AA genotype among osteoarthritis patients compared to the control group (P = 0.004). The number of affected hand joints was significantly higher among patients with ADAMTS14 AA genotype in comparison to patients with ADAMTS14 AG genotype (P = 0.002). In addition, AA genotype was associated with statistically significantly higher Kellgren-Lawrence radiological grades in the knee and hand joints (proximal interphalangeal and thumb interphalangeal joints) (P = 0.037, 0.003, and 0.030 respectively).ConclusionThe study showed an association between the AA genotype of ADAMTS14 gene rs4747096 single nucleotide polymorphism with knee and hand osteoarthritis and osteoarthritis severity in these joints. The AA genotype of ADAMTS14 gene rs4747096 single nucleotide polymorphism could be implicated in the increased incidence of primary osteoarthritis development and elevated disease severity among the Egyptian population.

The relationship between polymorphism of insulin-like growth factor I gene and susceptibility to type 2 diabetes in Uygur population, Xinjiang, China

BackgroundType 2 diabetes (T2DM) susceptibility varies among different populations and is affected by gene single nucleotide polymorphism (SNP). Insulin-like growth factor (IGF)-1 gene, which has many SNP loci, is involved in T2DM pathogenesis. However, the relationship of IGF-1 gene polymorphism with T2DM in Uyghur population is less studied.ObjectiveTo investigate the relationship between T2DM susceptibility and polymorphism of IGF-1 gene in Uyghur population of Xinjiang, China.MethodsThis study enrolled 220 cases (122 males (55.46%) and 98 females (44.54%); mean age of 53.40 ± 10.94 years) of T2DM patients (T2DM group) and 229 (124 males (54.15%) and 105 females (45.85%); mean age of 51.64 ± 10.48 years) healthy controls (control group). Biochemical indexes were determined. IGF-1 gene polymorphism was analyzed by SNP genotyping.ResultsThe levels of TG, HDL, LDL, BUN, and Cr were statistically significant between the T2DM group and the control group. In terms of IGF-1 polymorphism, T2DM group had higher frequency of AA genotype (OR = 2.40, 95% CI = 1.19–4.84) and allele A (OR = 1.55, 95% CI = 1.17–2.06) of rs35767 loci, suggesting that rs35767 is related to the occurrence of T2DM. A total of 5 gene interaction models was obtained through analyzing the interaction of 5 SNP loci with the GMDR method. Among them, the two-factor model that included rs35767 locus and rs5742694 locus had statistical difference with a large cross-validation consistency (10/10). The combination of GG/CC, GA/AA, AA/AA, and AA/AC genotype was in high-risk group, whereas the combination of GG/AA, GG/AC, GA/AC and GA/CC genotype was in the low-risk group. The risk of T2DM in the high-risk group was 2.165 times than that of the low-risk group (OR = 2.165, 95% CI = 1.478–3.171).ConclusionTG, HDL, LDL, BUN, and Cr are influencing factors of T2DM in Uyghur population. The rs35767 locus of IGF-1 gene may be associated with T2DM in Uyghur population. The high-risk group composing of rs35767 locus and rs5742694 locus has a higher risk of T2DM.

The impact of the nucleotide-binding oligomerization domain 1 (NOD 1) gene polymorphism on Helicobacter Pylori induced chronic gastritis in hepatic patients.

Background: Chronic infection with Helicobacter pylori (H.pylori ) causes atrophic and even gastric metaplastic changes, and it has a well-known link to peptic ulceration. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a protein receptor that is presented by the NOD1 gene. It distinguishes H.pylori bacterial molecules and enhances an immune response Objectives: to describe the relation between the NOD1 gene (rs2075820) polymorphism and H.pylori infection in hepatic and non hepatic patients with chronic gastritis, study its impact on the degree of chronic gastritis in H.pylori positive individuals, and to examine the effect of H. pylori on clinical, endoscopic and histopathological findings and child paugh scoring in hepatic patients. Methodology: Gastric tissue samples were taken from selected 200 patients with chronic gastritis, either hepatic or non hepatic. Rapid urease test and pathological findings classified them into H.pylori infected and non infected patients. Genotyping of NOD 1 was studied using polymerase chain reaction /restriction fragment length polymorphism (PCR–RFLP) method. Results: A significant higher frequency of AA genotype, and the A allele of NOD1 gene in H.pylori +ve patients, either hepatic; (58%)-(73%) or non hepatic;(62%)-(78%) as compared to H.pylori –ve patients,(P <0.001). A highly significant relation between NOD1 genotypes and endoscopic findings, where most of H.pylori infected patients with AA genotype had more peptic ulcer, antral erosion, gastric prolapse, esophageal varices and esophageal hiatus hernia compared to patients with GA and GG genotypes, (P<0.001). No significant impact of H.pylori on signs of liver affection and child paugh scoring in hepatic patients. Conclusions: In NOD1 gene polymorphism, AA genotype and A allele have significantly implicated in H.pylori infection susceptibility and progression. While GG genotype and G allele have a protective effect against H.pylori infection.

Gene polymorphisms of SOCS1 and SOCS2 and acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) causes the dysfunction of the systemic blood system and immune system. The etiology and predisposing factors of ALL are unknown. The suppressor of cytokine signaling 1 (SOCS1) and SOCS2 are inhibitors of cytokine signal transduction. Gene polymorphisms of SOCS1 and SOCS2 and their expressions may be related to ALL. A total of 200 ALL patients in our hospital and 200 healthy people were enrolled in ALL group and control group, respectively. Genomic deoxyribonucleic acids (DNAs) and total RNAs were extracted from the peripheral blood of each subject. Gene polymorphisms of SOCS1 at rs33977706, rs243327, and rs33932899 and those of SOCS2 at rs3816997 were amplified by polymerase chain reaction (PCR) and sequenced. Besides, the expression levels of SOCS1 and SOCS2 in ALL patients were detected by real-time fluorescence quantitative PCR. The frequency of the allele C of SOCS1 rs33977706 in ALL group was lower than that in the control group, displaying a significant difference between the two groups (p=0.015). The frequency of allele A of SOCS2 rs3816997 was notably higher in ALL group than that of the control group (p=0.000). In addition, the frequency of CA genotype of SOCS1 rs33977706 in ALL group was markedly lower than that in the control group, showing a significant difference (p=0.000). ALL group had remarkably higher frequencies of AA genotype of SOCS2 rs3816997 (p=0.000) and ACC haplotype of SOCS gene (p=0.000), and lower frequencies of ATG (p=0.026) and CCC (p=0.006) haplotypes. The two loci, SOCS1 rs33932899 and SOCS1 rs243327, were linked to each other (D'=0.781). Moreover, the expression level of SOCS1 in ALL group was lower than that in the control group, in which the expression of the CT genotype of SOCS1 rs243327 was relatively higher (p=0.021). SOCS2 level was lower in ALL group. Particularly, SOCS2 level in ALL patients carrying AC genotype was lower than those carrying AA and CC genotypes (p=0.000). ALL patients carrying CT genotype of SOCS1 rs243327 had shorter period of agranulocytosis (p=0.000), a lower ratio of bone marrow primitive/immature cells (p=0.001), and a higher hemoglobin (Hb) level in blood (p=0.000). The ratio of bone marrow primordial/immature cells was lower in ALL patients with AC genotype of SOCS2 rs3816997 (p=0.038). The expression levels of SOCS1 and SOCS2 are prominently related to ALL, and their polymorphisms are associated with the susceptibility to ALL.

Differential methylation of lncRNA KCNQ1OT1 promoter polymorphism was associated with symptomatic cardiac long QT.

To investigate whether the differential methylation of KCNQ1OT1 was associated with the risk of symptomatic long QTc. We investigated the methylation status of KCNQ1OT1 in a cohort of patients (n = 131) with a symptomatic prolonged QTc. All the patients were genotyped for a common promoter polymorphism (rs11023840). They were also genotyped for DNA digested with the methylation-sensitive HpaII restriction enzyme. We found a significant higher frequency of AA genotype (p = 0.02) in the patients compared with healthy controls (n = 240). In the HpaII-digested samples there was a higher frequency of the A-allele among the patients compared with the controls (p = 0.02). Our findings supported a role for the differential methylation/imprinting of KCNQ1OT1 in the risk for symptomatic prolonged QTc.

Association of -330 interleukin-2 gene polymorphism with oral cancer.

Background & objectives:Cytokines play an important role in the development of cancer. Several single-nucleotide polymorphisms (SNPs) of cytokine genes have been reported to be associated with the development and severity of inflammatory diseases and cancer predisposition. This study was undertaken to evaluate a possible association of interleukin 2 (IL-2) (− 330A>C) gene polymorphisms with the susceptibility to oral cancer.Methods:The SNP in IL-2 (−330A>C) gene was genotyped in 300 oral cancer patients and in similar number of healthy volunteers by polymerase chain reaction (PCR)-restriction fragment length polymorphism and the association of the gene with the disease was evaluated.Results:IL-2 (−330A>C) gene polymorphism was significantly associated with oral cancer whereas it was neither associated with clinicopathological status nor with cancer pain. The AC heterozygous genotype was significantly associated with oral cancer patients as compared to controls [odds ratio (OR): 3.0; confidence interval (CI): 2.14-4.20; P<0.001]. The C allele frequency was also significantly associated with oral cancer (OR: 1.80; CI: 1.39-2.33; P<0.001). IL-2 (−330A>C) gene polymorphism was also associated with oral cancer in tobacco smokers and chewers.Interpretation & conclusions:Our results showed that oral cancer patients had significantly higher frequency of AA genotype but significantly lower frequency of AC genotype and C allele compared to controls. The IL-2 AC genotype and C allele of IL-2 (−330A>C) gene polymorphisms could be potential protective factors and might reduce the risk of oral cancer in Indian population.

A meta-analysis of three identified single nucleotide polymorphisms at 1p13.3 and 1q41 and their associations with lipid levels and coronary artery disease

The aim of this meta-analysis was to detect whether three identified single nucleotide polymorphisms (SNPs) (rs646776, rs599839, and rs17465637) at 1p13.3 and 1q41 are associated with lipid levels and the risk of coronary artery disease (CAD). Databases of MEDLINE, EMBASE, the Cochrane Library, and BIOSIS were systematically searched. The pooled effects were expressed as odds ratio or standardized mean difference or mean difference with 95% confidence intervals. A total of 14 studies with 57,916 patients were included in the meta-analysis. Pooled effects showed that the AA group of 1p13.3 rs599839 had higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC), and lower high-density lipoprotein cholesterol (HDLC) levels than the GA/GG group, and the CAD group had higher AA genotype frequency than the control group. The TT group of 1p13.3 rs646776 had higher TC and LDLC levels and lower HDLC levels than the CT/CC group. The CAD group also had higher CC genotype frequency of 1q41 rs17465637 than the control group. The SNPs of 1p13 rs599839 and rs646776 were associated with serum lipid levels. The genetic variants of 1p13 rs599839 and 1q41 rs17465637 SNPs were prominently related to CAD, and the genetic variants of chromosome 1p13 promote the risk of CAD by increased TC and LDLC levels and decreased HDLC levels.

The Association Between Viral Infections and Co-stimulatory Gene Polymorphisms in Kidney Transplant Outcomes.

BackgroundThe surveillance of kidney transplant patients depends on function of different immunologic markers like co-stimulatory molecules. These molecules may also be associated with post kidney transplant viral related outcomes.ObjectivesThe aim of this study was to investigate the possible associations between co-stimulatory molecule gene polymorphisms and viral infections in kidney transplant patients.Patients and MethodsIn total, 172 kidney transplant patients were included in this study. Single nucleotide polymorphisms in loci of co-stimulatory molecules including: PDCD.1, CD28, CTLA4 and ICOS, were analyzed in the studied patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Active Cytomegalovirus (CMV) infection and history of hepatitis C virus (HCV) infection were analyzed in each kidney transplant patient using the CMV antigenemia kit and HCV antibody assay, according to the manufacturer’s instructions.ResultsCMV active infection was found in 31 of 172 (18.02%) kidney transplant patients. HCV infection was only found in two of the 172 (1.16%) studied patients. Significant associations were found between TT and TC genotypes of CTLA4 -1722T/C and T allele with acute rejection in CMV infected kidney transplant patients. A significant association was also found between the T allele of CD28 + 17 C/T genetic polymorphism and acute rejection in CMV infected kidney transplant patients. Significantly higher frequency of AA genotype and A allele of CTLA4 + 49AG polymorphism were found in CMV infected female patients. Also a significantly higher frequency of GG genotype and G allele of PDCD-1.3A/G polymorphisms were found in CMV infected female patients.ConclusionsBased on these results, CTLA4 and CD28 genetic polymorphisms, which regulate T-cell activation, can influence active CMV infection in kidney transplant patients. These results should be confirmed by further investigations.

Association between DCHS2 gene and mild cognitive impairment and Alzheimer's disease in an elderly Brazilian sample.

In 2012, Kamboh and colleagues published a genome-wide association study that identified the DCHS2 gene (rs1466662 T/A) influencing the age at onset of Alzheimer's disease (AD). We aimed to investigate if there is association between the DCHS2 gene and amnestic mild cognitive impairment (aMCI) and AD in a sample of the Brazilian population. 143 controls, 79 aMCI and 299 AD patients were selected and submitted to the same protocol of tests. Genotyping was performed using the Real Time PCR RESULTS: Amnestic MCI patients showed a higher prevalence of AA than controls and a lower frequency of TT when compared with controls. We also stratified the sample according to the APOE ε4 status. No difference in DCHS2 genotype or allelic frequency occurred in the APOE ε4 allele carrier subgroup. Amnestic MCI patients showed a higher frequency of AA genotype and a lower frequency of TA and TT when compared with controls in APOE ε4 allele non-carrier subgroup. The allelic distribution followed the same pattern. In AD group, we observed a significant difference with a higher A allelic frequency in AD in this subgroup. A multiple logistic regression demonstrated that in APOE ε4 non-carriers, allele rs1466662 was associated to aMCI group. Different variables were associated with aMCI and AD according to APOE ε4 status in our sample. Low level of education was associated with AD, while diabetes mellitus type 2 was associated with aMCI. Copyright © 2016 John Wiley & Sons, Ltd. Our findings suggest a possible role for DCHS2 gene in aMCI and AD.

Polymorphisms in endothelial nitric oxide synthase gene in early and late severe preeclampsia

Preeclampsia (PE) is characterized by hypertension and proteinuria, occurring after the 20th week of pregnancy in women who have had no previous symptoms. The disease progresses with generalized vasoconstriction and endothelial dysfunction. Clinically, it is important to diagnose the severe form of the disease (sPE), in which blood pressure and proteinuria are much higher. Recently, the gestational age (GA) of the onset of PE has led to the classification of this disease as early (GA <34 weeks) and late (GA ≥34 weeks). Several genetic polymorphisms affecting endothelial nitric oxide synthase (eNOS) levels or function were described, including G894T (Glu298Asp), VNTR b/a (variable-number 27-bp tandem repeat) and T-786C (promoter) polymorphisms. Thus, the aim of this study was to compare the distribution of G894T, VNTR b/a and T-786C polymorphisms and their haplotypes in Brazilian early and late sPE, as well as in normotensive pregnant. A total of 201 women were evaluated, 53 with early sPE, 45 with late sPE and 103 as normotensive pregnant women. The frequency of 894T allele was higher in late sPE vs normotensive pregnant, and 894TT genotype was higher in late sPE vs early sPE and normotensive pregnant. For VNTR b/a polymorphism, higher frequencies of aa genotype and a allele were observed in early sPE vs late sPE and normotensive pregnant. Besides, the frequency of haplotype T-b-C was higher in late sPE vs early sPE and normotensive pregnant. Considering the results found for eNOS polymorphisms, it is possible to suggest that the functional alterations induced by these two polymorphisms may influence the time of severe PE onset, although both alterations are putatively associated with low NO bioavailability. However, other studies are necessary to validate these findings and clarify this issue.

AT2R -1332 G:A polymorphism and diabetic nephropathy in type 2 diabetes mellitus patients.

Introduction: The rennin-angiotensin system (RAS) plays a central role in the regulation of sodium metabolism, vascular tone, blood pressure, renal hemodynamics, and vascular modeling and is activated by hyperglycemiaObjectives: In the present study the influence of AT2R -1332 G:A polymorphism on the risk of T2DM and its complications in a population from Western Iran has been investigated. Patients and Methods: In a case-control study, 70 individuals with type 2 diabetes mellitus (T2DM) including normo-, micro- and macro-albuminuric patients and 112 healthy subjects from the Kermanshah province were studied to investigate the association between the angiotensin type 2 receptor (AT2R) -1332 G:A variants with the risk of T2DM and its complications. The genotypes of the AT2R were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Analysis of AT2R -1332 G:A polymorphism indicated the absence of association between this polymorphism with T2DM and diabetic nephropathy. Results: Analysis of AT2R -1332 G:A polymorphism indicated the absence of association between this polymorphism with T2DM and diabetic nephropathy. In females with diabetic nephropathy a significantly higher frequency of AA genotype (50%) was detected compared to those without nephropathy (13.3%, p=0.015). The presence of A allele of AT2R was associated with significantly (p=0.029) increased risk of coronary artery disease (CAD) in diabetic patients without nephropathy. Conclusion: Our study indicated an association between the AT2R -1332 G:A polymorphism and the risk of diabetic nephropathy in females only. Also, the A allele was associated with the risk of CAD in those diabetic patients without nephropathy.

Genetic variability at IMPA2, INPP1 and GSK3β increases the risk of suicidal behavior in bipolar patients

Bipolar patients (BP) are at high risk of suicide. Causal factors underlying suicidal behavior are still unclear. However, it has been shown that lithium has antisuicidal properties. Genes involved in its putative mechanism of action such as the phosphoinositol and the Wnt/β-catenine pathways could be considered candidates for suicidal behavior (SB). Our aim was to investigate the association of the IMPA1 and 2, INPP1, GSK3α and β genes with suicidal behavior in BP.199 BP were recruited. Polymorphisms at the IMPA1 (rs915, rs1058401 and rs2268432) and IMPA2 (rs66938, rs1020294, rs1250171 and rs630110), INPP1 (rs3791809, rs4853694 and 909270), GSK3α (rs3745233) and GSK3β (rs334558, rs1732170 and rs11921360) genes were genotyped. All patients were grouped and compared according to the presence or not of history of SB (defined as the presence of at least one previous suicidal attempt). Single SNP analyses showed that suicide attempters had higher frequencies of AA genotype of the rs669838-IMPA2 and GG genotype of the rs4853694-INPP1gene compared to non-attempters. Results also revealed that T-allele carriers of the rs1732170-GSK3β gene and A-allele carriers of the rs11921360-GSK3β gene had a higher risk for attempting suicide. Haplotype analysis showed that attempters had lower frequencies of A:A haplotype (rs4853694:rs909270) at the INPP1 gene. Higher frequencies of the C:A haplotype and lower frequencies of the A:C haplotype at the GSK-3β gene (rs1732170:rs11921360) were also found to be associated to SB in BP.Therefore, our results suggest that genetic variability at IMPA2, INPP1 and GSK3β genes is associated with the emergence of SB in BP.

A Functional Polymorphism in the Epidermal Growth Factor Gene Is Associated with Risk for Glioma in a Chinese Population

Epidermal growth factor (EGF) plays a key role in survival of neural and glial precursor cells. A single nucleotide polymorphism of the EGF gene +61G/A in the 5'-untranslated region has been reported to be associated with susceptibility to glioma. The purpose of this study was to investigate the potential association between EGF +61G/A and brain glioma in a Chinese population. A case-control study involving 180 patients with glioma and 360 controls was done. Polymerase chain reaction restriction fragment-length polymorphism assay was used to analyze the EGF +61G/A genotypes. Patients with glioma had a significantly higher frequency of AA genotype (odds ratio, 2.25; 95% confidence interval, 1.20, 4.21; p=0.01] than controls. When stratified by histologic features and World Health Organization grade of glioma, distribution of each genotype did not significantly differ. Our data suggested that the EGF +61G AA genotype was associated with a higher glioma risk in a Chinese population. This finding is in contrast with previous studies that reported the G allele as a risk factor for glioma in white patients.

BsmI, TaqI, ApaI, and FokI polymorphisms in the vitamin D receptor gene and periodontitis: a meta-analysis of 15 studies including 1338 cases and 1302 controls

A meta-analysis was conducted in order to investigate the potential association of vitamin D receptor (VDR) gene polymorphisms with susceptibility to aggressive and chronic periodontal disease. A database search yielded a total of 15 studies involving 1338 cases and 1302 controls. Four polymorphisms were included in the meta-analysis: VDR TaqI (rs731236), VDR BsmI (rs1544410), VDR FokI (rs2228570), and VDR ApaI (rs7975232). Odds ratios (ORs) along with their 95% confidence intervals (CIs) were computed to compare the distribution of alleles and genotypes between cases and controls. The combined results based on all studies showed that (1) chronic periodontitis cases had a significantly lower frequency of bb genotype of BsmI [OR=0.63, 95% CI=0.42, 0.94; p=0.02] in Asians; (2) chronic periodontitis cases had a significantly higher frequency of AA genotype of ApaI (OR=2.20, 95% CI=1.39, 3.48; p<0.001) in Asians; (3) chronic periodontitis cases had a weak significantly higher frequency of TT genotype of TaqI (OR=1.86, 95% CI=1.002, 3.46; p=0.049) in Asians. After Bonferroni's correction, we found that in Asians chronic periodontitis cases still had a significantly higher frequency of AA genotype of ApaI. No significant difference was found in any genotype of FokI. No association was found for all the VDR gene polymorphisms examined as far as the aggressive form of the disease is concerned. Future studies need to focus on the possible biological consequences and mechanisms of the VDR genetic variants. The current findings confirm that VDR gene is a candidate gene for periodontitis.

BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and risk of fracture in Caucasians: A meta-analysis

Context Vitamin D receptor (VDR) gene polymorphisms have been strongly associated with bone mineral density in some studies. However, in a recent meta-analysis, no relationship of the VDR BsmI or TaqI polymorphism and fracture risk was found in the meta-analysis of published data. Objective and design Our meta-analysis studied whether a relationship exists between BsmI, TaqI, ApaI and FokI polymorphisms in the VDR gene and risk of fracture. Data sources Relevant studies were identified from the following electronic databases: MEDLINE, EMBASE and Current Contents before January 2010. Data synthesis This meta-analysis included 17 studies with a total of 21 eligible comparisons, which included 2112 fracture cases and 4521 controls. All of these studies reported on Caucasians. The combined results based on all studies showed that fracture cases had a significantly lower frequency of bb genotype of BsmI [odds ratio (OR) = 0.87, 95% confidence interval (CI) = 0.76, 0.98]. When stratifying by fracture type, we found that (1) hip fracture cases had a significantly lower frequency of bb genotype of BsmI (OR = 0.82, 95% CI = 0.70, 0.97); (2) hip fracture cases had a significantly lower frequency of Tt genotype of TaqI (OR = 0.65, 95% CI = 0.43, 0.97); (3) hip fracture cases had a significantly higher frequency of tt genotype of TaqI (OR = 1.74, 95% CI = 1.05, 2.91); (4) vertebral fracture cases had a significantly higher frequency of Aa genotype of ApaI (OR = 1.63, 95% CI = 1.03, 2.59). No significant difference was found in any genotype of FokI. Conclusion Our meta-analysis suggests that there is a modest but statistically significant association between the BsmI bb genotypes and fracture.

Impact of matrix metalloproteinase-1 gene variations on risk of acute coronary syndrome

This case-control study was conducted to investigate whether genetic variations in the matrix metalloproteinase-1 gene promoter were related to risk of acute coronary syndrome (ACS). 222 patients with ACS and 191 normal controls were examined by means of polymerase chain reaction (PCR) and restriction fragment length polymorphism. A significantly higher frequency of AA genotype of -519A/G polymorphism was observed in ACS patients than in the controls (P<0.001). The relative risk of ACS in patients carrying A allele of -519A/G polymorphism was 1.33 [P<0.001, 95% confidence interval (CI)=1.12-1.57]. Linkage disequilibrium test and haplotype analysis indicated that the AT haplotype significantly increased the risk of ACS (P=0.004, 95% CI=1.14-2.04, odds ratio=1.53). Compared with the AT haplotype, the GT haplotype was associated with a reduced occurrence of ACS (P<0.001, 95% CI=0.36-0.70, odds ratio=0.51). Our findings suggested that genetic variations in the matrix metalloproteinase-1 gene promoter may contribute to interindividual variability in risk of ACS, and help predict susceptible individuals.

Single-nucleotide polymorphisms of the interleukin-18 gene promoter region in rheumatoid arthritis patients: protective effect of AA genotype.

Rheumatoid arthritis (RA) is a chronic arthritic condition that can lead to deformities and disabilities. Although numerous studies reported the association of human leukocyte antigen (HLA)-DRB1*04 and RA, other genes, e.g. cytokines genes, may contribute towards disease susceptibility. Interleukin-18 (IL-18) is a proinflammatory cytokine postulated to play a role in the acute and chronic inflammatory phases of RA. The IL-18 protein expression seems to be regulated by two single-nucleotide polymorphisms (SNPs) located at positions -607 and -137 in the promoter region of the gene. It is postulated that specific alleles may be associated with susceptibility to the development of RA. In the present study, we described the IL-18 gene promoter region genotypes and combined genotypes (-607/-137) in 106 RA patients and 273 unrelated healthy controls to evaluate the contributions of these alleles to RA predisposition in Chinese, Malays, and Indians. The genotyping were performed using sequence-specific polymerase chain reactions. Rheumatoid factors were assayed by enzyme-linked immunosorbent assay. Biodata were obtained through chart review. The controls had significantly higher frequency of AA genotype at position -607 when compared to RA patients. No significant differences were observed in the distribution of either allelic or genotypic frequencies at position -137. There was no association between the genotypes and the presence of rheumatoid factors. This study did not find evidence of a genetic susceptibility factor but demonstrated the novel finding that the AA genotype at position -607 is associated with a protective effect against development of RA in Chinese individuals. This protection may be mediated through inhibition of cyclic (Adenosine 3', 5'-cyclic monophosphate) AMP-responsive element (CRE)-binding protein by the disruption of the CRE consensus sequence.

Cyclin D1 gene polymorphism and susceptibility to lung cancer in a Chinese population.

The objective was to study the relationship between cyclin D1 gene (CCND1) polymorphism and lung cancer in the Chinese population. Blood samples of 182 cases and 185 controls were collected from a hospital based case-control study. PCR-SSCP was used to examine the G/A polymorphism in exon 4 of CCND1. The results showed that the frequencies of the CCND1 AA, GA and GG genotypes were 31.3, 46.7 and 22.0% respectively in cases, and 21.1, 53.0 and 25.9 respectively in controls. Adjusted by age (in years), sex and smoking status, multivariate logistic regression analysis showed that the AA genotype was associated with a significantly increased risk (OR = 1.87, 95% CI 1.01-3.45) for lung cancer. In the stratification analysis, the CCND1 AA variant genotype was associated with increased risk in individuals who were </=50 years old (OR = 3.23, 95% CI 1.17-8.96) and males (OR = 2.46, 95% CI 1.18-5.10). According to histological types, there was significantly higher frequency of AA genotype in squamous cell lung cancer than that in controls (OR = 2.92, 95% CI 1.07-8.03). In conclusion, it is suggested that the CCND1 G/A polymorphism is associated with the early onset of lung cancer in men and contributes to susceptibility to lung cancer, especially squamous cell cancer, in this population.