Lack of association between G‐protein coupled receptor kinase 5 gene and Parkinson's disease

The major component of Lewy Bodies (LB), the pathological hallmark of Parkinson's disease (PD) is α‐synuclein, most prominently phosphorylated at serine 129. G‐protein coupled receptor kinase 5 (GRK5) has been reported to phosphorylate α‐synuclein in vitro, enhancing the α‐synuclein toxicity to dopaminergic neurons in Drosophila model. Moreover, GRK5 was found in LBs from brain of PD patients. A genetic association study performed in the Japanese population revealed haplotypic association of the GRK5 gene with susceptibility to sporadic PD. We aimed at investigating whether four polymorphisms within the GRK5 gene (rs871196, rs2420616, rs7069375, rs4752293) could represent a risk factor for sporadic PD in Southern Italy. We genotyped 446 patients with PD and 450 controls for these markers and did not find any significant association with the disease at allelic, genotypic and haplotypic level. Our results indicate that the GRK5 gene does not confer risk to sporadic PD in our sample from Southern Italy. © 2010 Wiley‐Liss, Inc.     

DJ-1基因多态性与四川地区散发性帕金森病的相关性研究

目的 了解DJ-1基因3个多态位点(g.168-185del;SNP405,refSNPID:rs3766606;293G/A)的频率以及与帕金森病的相关性.方法 采用病例-对照研究,应用聚合酶链反应-限制性片段长度多态性及DNA测序等技术对192例帕金森病患者和198名对照者的3个位点进行基因型的检测.结果 在g.168-185del位点,研究人群中Ins/Ins基因型较普遍,等位基因Del的频率很低(0.38%);在所检测的人群中未发现293G/A的多态性.上述结果与欧美国家的报道不一致.在SNP405 G/T多态位点中,在发病年龄小于40岁的帕金森患者群中G/T基因型频率显著高于对照组(18.75%vs5.54%,P=0.004,OR=6.30,95%CI:1.96～20.18).结论 g.168-185del和293G/A两多态性位点的频率在中国人群与欧美人群间可能存在差异;非翻译区SNP405 G/T多态性可能增加早发帕金森病的发病风险.     

Association between three functional polymorphisms of dopamine D2 receptor gene and tardive dyskinesia in schizophrenia

The dopamine D2 receptor (DRD2) gene is considered one of the candidate genes contributing to the development of tardive dyskinesia (TD). In the present study, we investigated the genetic association between three functional polymorphisms (Ser311Cys, ?141C Ins/Del and TaqI A) in the DRD2 gene and TD (200 patients with schizophrenia: 44 with TD and 156 without TD). No significant difference in the allelic and genotypic distribution between patients with TD and those without TD was observed. However, we found a slightly significant association between the ?141C Ins/Del polymorphism and the total Abnormal Involuntary Movement Scale (AIMS) score (P = 0.037). The significant association between the ?141C Ins/Del polymorphism and the total AIMS score did not remain after the regression analysis was taken into account (P = 0.14). Our results suggest that that three functional polymorphisms in DRD2 may not play a major role in the occurrence of TD. © 2001 Wiley‐Liss, Inc.     

HLA-G susceptibility to hepatitis B infection and related hepatocellular carcinoma in the Japanese population

AimsHuman leukocyte antigen (HLA)-G plays a role in various physiological immunomodulatory functions. Aberrant HLA-G expression is observed in various disease states, including tumors, autoimmune disorders, and viral infections. The present study investigated the association between HLA-G functional gene polymorphisms (rs1736933 [-486 C > A], rs1049033 [+2018 C > T], 14 bp Insertion [Ins]/Deletion [Del] [+2961 Del > Ins], and rs1063320 [+3142 C > G]) and disease susceptibility, hepatocellular carcinoma (HCC) development, and hepatitis B surface antigen (HBsAg) clearance.MethodsAllele discrimination of the 3 SNPs (-486 C > A, +2018 C > T, +3142 C > G) was determined by a TaqMan 5′ exonuclease assay, while the 14 bp Ins/Del polymorphism was typed by fragment analysis using Genetic Analyzer and GeneMapper software. The above polymorphisms were analyzed for 325 Japanese hepatitis B virus (HBV) patients, 355 Japanese healthy subjects (Controls) as healthy controls, and 799 Japanese hepatitis C virus (HCV) patients as disease controls, respectively.ResultsThe 14 bp Insertion allele was significantly more frequent in HBV patients than Controls (27.1 % vs 20.6 %, odds ratio [OR] 1.43, P = 0.005) but did not differ between HCV patients and Controls. Similar results were found for the rs1063320 G allele (38.9 % vs 26.3 %, OR 1.78, P < 0.001) and the rs1736933 T allele (32.2 % vs 26.9 %, OR 1.29, P = 0.034) between HBV and Controls. The rs1049033 T allele showed a weak but significant association with HCC development in the dominant model (OR 1.95, P = 0.04). Regarding HBsAg clearance, the A allele at rs1736933 was significantly correlated in the recessive model (OR 3.23, P = 0.003).ConclusionsThis study revealed significant associations of HLA-G gene polymorphisms with disease susceptibility, HCC development, and HBsAg clearance in HBV patients.     

HLA‐G gene 14‐bp deletion variant protects Iranian subjects against chronic hepatitis B infection

To investigate whether 14‐bp Ins/Del polymorphism in HLA‐G gene is associated with the risk of chronic hepatitis B (CHB) infection. This study was performed on a total of 396 individuals including 199 CHB patients and 197 healthy subjects from a south‐east Iranian population. We genotyped 14‐bp Ins/Del polymorphism in the HLA‐G gene using polymerase chain reaction method. The results of our study revealed that the HLA‐G 14‐bp deletion polymorphism was associated with a reduced risk of CHB at both allele and genotypic levels. The 14‐bp Del allele and Ins/Del genotype were more frequent in control group than in CHB patients (37% vs 28% for Del allele with OR = 0.68 and p‐value = .015; 73% vs 52% for Ins/Del genotype with OR = 0.43 and p‐value = .001) and both were protective factors against CHB. However, no difference was found in the distribution of HLA‐G 14‐bp genotypes among subjects with varied levels of HBV DNA or hepatic enzymes (p > .05). Our findings, for the first time, suggest that the HLA‐G 14‐bp Ins/Del polymorphism may be a marker for genetic susceptibility to CHB infection.     

Screening for two SNPs of LINGO1 gene in patients with essential tremor or sporadic Parkinson's disease in Chinese population

Two markers rs9652490 and rs11856808 both located in intron 3 of the LINGO1 gene have been nominated recently to be associated with essential tremor (ET). Although ET and Parkinson's disease (PD) are considered as different entities, they have many overlapping clinical and pathological features. We aimed to evaluate the role of rs9652490 and rs11856808 in the development of ET and PD. To this point, we sequenced the region involving the two markers in 109 ET cases, 425 sporadic Parkinson's disease (SPD) cases and 430 controls in Chinese population. After stratification by age, the rs9652490G allele suggested protective role in the early onset PD (EOPD, age at onset ≤50 years) group compared with age matched controls (OR = 0.56, 95% CI: 0.35–0.90, p = 0.015). No other significant association was found. We concluded that the two markers rs9652490 and rs11856808 were not strongly related to the development of ET or late onset SPD, but the rs9652490G allele might be a protective factor for EOPD in Chinese population.     

Association of RGS2 variants with panic disorder in a Japanese population

Panic disorder (PD) is a severe and chronic psychiatric disorder with significant genetic components underlying its etiology. The gene regulator of G protein signaling 2 (RGS2) has been reported to be associated with anxiety disorders. To confirm the association of RGS2 with PD, we investigated three single nucleotide polymorphisms (SNPs) of RGS2 (rs10801152, rs4606, and rs1819741) in 677 Japanese PD cases and 460 controls. The SNP rs10801152 was suggestive of an association with PD (allele P = 0.045 adjusted using sex and age as confounding factors). The three‐SNP haplotype was significantly associated with PD (global permutation P = 4 × 10^?4). The haplotypes T‐G‐C and T‐C‐T showed significant association and protective effect on PD (T‐G‐C, permutation P = 0.038, OR = 0.80, 95%CI = 0.68–0.95; T‐C‐T, permutation P = 0.004, OR = 0.38, 95%CI = 0.21–0.70). These results provide support for an association of RGS2 with PD in a Japanese population. © 2011 Wiley‐Liss, Inc.     

Human leucocyte antigen‐G 14‐bp InDel polymorphism and oral squamous cell carcinoma risk in Chinese Han population: A case–control study

Human leucocyte antigen‐G (HLA‐G) is a nonclassical HLA class I molecule involved in tumour immune escape. The purpose of this study was to investigate the association between the 14‐bp insertion/deletion (InDel) polymorphism in the 3′ untranslated region (3′‐UTR) of HLA‐G gene and oral squamous cell carcinoma (OSCC) risk in Chinese Han population (216 cases and 193 healthy controls), and furthermore, to evaluate serum soluble HLA‐G (sHLA‐G) levels in the OSCC patients. Our results demonstrated that the Ins allele was significantly less frequent in the OSCC patients than that in the healthy controls (odds ratio [OR] = 0.75; 95% confidence interval [CI]: 0.57–0.99; p = 0.040). Distribution of the 14‐bp genotypes in the OSCC patients and the healthy controls revealed that the Ins/Ins genotype was associated with decreased OSCC risk in both the codominant model (Ins/Ins versus Del/Del; OR = 0.57; 95% CI = 0.33–0.99; p = 0.044) and the log‐additive model (OR = 0.76; 95% CI: 0.58–0.99; p = 0.044). The serum sHLA‐G level was significantly higher in the OSCC patients than those in the healthy controls (p < 0.001). Receiver operating characteristic (ROC) curve revealed the valuable diagnostic value of sHLA‐G for OSCC detection, with an area under the ROC curve (AUC) of 0.891 (95% CI: 0.856–0.925, p < 0.001). The OSCC patients with Ins/Ins genotype had lower serum sHLA‐G levels than those with Ins/Del and Del/Del genotypes (p = 0.015). Furthermore, serum sHLA‐G levels were significantly increased with the increasing TNM stages of the OSCC patients (p = 0.017). Our findings revealed that the HLA‐G 14‐bp InDel polymorphism might be a genetic risk factor for OSCC susceptibility, and the serum sHLA‐G may act as a promising biomarker for noninvasive diagnosis of OSCC.     

Association of GWAS loci with PD in China

Genome‐wide association studies (GWAS) have identified numerous single‐nucleotide polymorphisms (SNPs) at four loci (SNCA, PARK16, LRRK2, BST1) that can modulate the risk of Parkinson's disease (PD). The strength of these associations has yet to be clarified in Mainland China. Ethnic specific effect is an important consideration in GWAS analysis. Using a case–control methodology, we genotyped multiple SNPs at these four loci to investigate their association with risk of PD in Mainland China. A total of 1,146 study subjects comprising 636 patients with PD and 510 unrelated healthy controls were recruited. The minor alleles at SNPs rs894278, rs1994090, rs2046932, rs4698412, and rs7304279 were found to be significantly higher in cases than in controls, while the minor alleles were found to significantly reduce the risk of developing PD at SNPs rs823128, rs823156, rs6532194, rs1191532, and rs16856139. These associations remained after taking into considerations the effects of age and gender. We showed that multiple SNPs at LRRK2 and SNCA increase risk of PD, while PARK16 SNPs are associated with a lower risk of PD in China. Our study findings will contribute to further research using GWAS‐linked data and research on ethnic specific effect of common variants. © 2011 Wiley‐Liss, Inc.     

Promising link of HLA-G polymorphism,tobacco consumption and risk of Head and Neck Squamous Cell Carcinoma (HNSCC) in North Indian population

Human leukocyte antigen (HLA-G) is a potent immune-tolerant molecule and has a critical role in various pathological conditions of cancer. The aim of the study was to analyze the association of HLA-G polymorphism as a risk factor in Head and Neck Squamous Cell Carcinoma (HNSCC). The HLA-G polymorphism at 3′UTR 14bp INDEL (rs371194629) and +3142G/C (rs1063320) were studied in 383 HNSCC patients and 383 ethnically similar-aged healthy controls in North Indian population. The genotyping study of two polymorphisms of HLA-G was documented using DNA-PAGE and RFLP-PCR method. 14bp INDEL Del/Ins, Ins/Ins genotype and Ins allele were more pronounced in HNSCC patients in compared to controls. Whereas, +3142 C/C genotype and C allele were associated with risk factors in HNSCC. Furthermore, the dual effect of polymorphisms; both variants (Del/Ins-Ins/Ins & G/C-C/C) carrying loci was significantly (OR = 2.78) associated with the disease compared to one variant (Del/Del-G/C or Del/Del-C/C or Ins/Ins-G/G). Moreover, both polymorphisms showed promising link in terms of tobacco influence on HNSCC risk. It can be concluded that this study first time reports that C/C, Del/Ins and Ins/Ins genotype as well as C and Ins allele could be major risk factors with strong impact of tobacco for HNSCC in North Indian population.     

Allelic association analysis of the dopamine D2, D3, 5‐HT2A,and GABAAγ2 receptors and serotonin transporter genes with heroin abuse in Chinese subjects

Five candidate genes, the receptors DRD2, DRD3, HTR2A and GABA_Aγ2, and the serotonin transporter (5‐HTT) were analyzed for association with heroin abuse. We examined three polymorphisms (promoter ? 141ΔC, Ser311Cys, and TaqI) in the DRD2 gene, one polymorphism (Ser9Gly) in the DRD3 gene, two polymorphisms (promoter ? 1438G/A and T102C) in the HTR2A gene, two polymorphisms (VNTR and Del/Ins) in 5‐HTT gene, and one polymorphism (G3145A) in GABA_Aγ2 gene in 121 Chinese heroin addicts and 194 controls. None of the polymorphisms differed significantly for allele, genotype, or haplotype frequencies, except for the DRD2 promoter polymorphism ? 141ΔC (genotype‐wise and allele‐wise, P = 0.05, uncorrected). An additional 344 subjects with heroin abuse and 104 controls were investigated for the ? 141ΔC polymorphism. In the second sample, there were no significant difference of genotype or allele frequencies between subjects with heroin abuse and normal controls. When we divided the sample by route of administration into nasal inhalers and IM or IV injectors, however, it produced a significant difference between inhalers of heroin and controls (genotype‐wise, P = 0.006, allele‐wise, P = 0.016) but not for injectors of heroin (genotype‐wise, P = 0.81, allele‐wise, P = 0.69). We also found that LD between all polymorphisms we examined in the gene was weak, possibly explaining why we see association of this polymorphism with heroin abuse but not with other markers in the gene. Overall our results indicates that the HTR2A, 5‐HTT, DRD3 and GABA_Aγ2 genes are not likely to be a major genetic risk factor for heroin abuse in this population, with the exception of possible association between nasal inhalation and DRD2 promoter ? 141ΔC polymorphism. © 2002 Wiley‐Liss, Inc.     

Genetic analysis of “leucine‐rich repeat (LRR) and immunoglobulin (Ig) domain‐containing,Nogo receptor‐interacting protein‐1 (LINGO1)” in two independent Chinese parkinson's disease populations

A large genome‐wide association study has shown that the “leucine‐rich repeat (LRR) and immunoglobulin (Ig) domain‐containing, Nogo receptor‐interacting protein‐1 (LINGO1) gene” is associated with an increased risk for essential tremor (ET) recently. Given the clinical phenotype overlap between Parkinson's disease (PD) and ET, and LINGO1 had also been demonstrated to play roles in the structural plasticity and integrity of the DA neurons as well as survival of dopaminergic neurons in PD animal models, it has been suggested that the LINGO1 variant could be associated with PD. Here, we report the first analysis of the LINGO1 variant rs9652490 (A > G) in two independent case–control cohorts in ethnic Chinese populations involving a total of 1,305 subjects (649 PD patients and 656 controls) from Taiwan and Singapore. We were unable to demonstrate any significant association between genotype distribution and allele frequency with risk of PD in each case–control study and in the pooled analysis. Further meta‐analysis including all published data and ours failed to demonstrate any modulatory role of rs9652490 GG genotype or G allele. LINGO1 variant rs9652490 (A > G) is unlikely to play a major role in PD in our Chinese populations. © 2010 Wiley‐Liss, Inc.     

Unexpected mitochondrial matrix localization of Parkinson's disease‐related DJ‐1 mutants but not wild‐type DJ‐1

DJ‐1 has been identified as a gene responsible for recessive familial Parkinson's disease (familial Parkinsonism), which is caused by a mutation in the PARK7 locus. Consistent with the inferred correlation between Parkinson's disease and mitochondrial impairment, mitochondrial localization of DJ‐1 and its implied role in mitochondrial quality control have been reported. However, the mechanism by which DJ‐1 affects mitochondrial function remains poorly defined, and the mitochondrial localization of DJ‐1 is still controversial. Here, we show the mitochondrial matrix localization of various pathogenic and artificial DJ‐1 mutants by multiple independent experimental approaches including cellular fractionation, proteinase K protection assays, and specific immunocytochemistry. Localization of various DJ‐1 mutants to the matrix is dependent on the membrane potential and translocase activity in both the outer and the inner membranes. Nevertheless, DJ‐1 possesses neither an amino‐terminal alpha‐helix nor a predictable matrix‐targeting signal, and a post‐translocation processing‐derived molecular weight change is not observed. In fact, wild‐type DJ‐1 does not show any evidence of mitochondrial localization at all. Such a mode of matrix localization of DJ‐1 is difficult to explain by conventional mechanisms and implies a unique matrix import mechanism for DJ‐1 mutants.     

HLA‐G 14‐bp Ins/Ins Genotype in Patients Harbouring Helicobacter pylori Infection: A Potential Risk Factor?

H. pylori is a potent pathogen due to its capacity to successfully evade host defence mechanisms. Despite inducing immune responses in infected individuals, sometimes these responses fail to clear the infection and the bacterium establishes a persistent infection leading to chronic inflammation. In this context, we hypothesized that human leucocyte antigen G (HLA‐G), a non‐classical major histocompatibility complex molecule that has the ability to regulate immune responses both in physiological and in pathological conditions, may play an important role in promoting tolerance and helping H. pylori to subvert host defence and consequently establish a chronic infection. Therefore, we evaluated the expression of HLA‐G 14‐bp Ins/Del polymorphism in patients harbouring H. pylori infection, as well as their relationship with histological and demographic variables, to gain a better understanding of the actual role of HLA‐G and its genetic polymorphisms in bacterial infection. Sixty‐eight patients with clinical symptoms suggestive of H. pylori infection were enrolled to assess HLA‐G 14‐bp Ins/Del polymorphism allele and genotype frequencies. After adjustment for covariates (age and gender), the odds of having the genotype Ins/Ins, compared to Del/Del, were 3.77 times greater among HP+ cases than among controls. These findings suggest that the 14‐bp Ins/Ins genotype, already associated with inflammatory and autoimmune diseases as well as some viral and parasitic infections, could confer a greater risk of developing H. pylori infection.     

Lack of replication of a previously reported association between polymorphism in the 3′UTR of the alpha-synuclein gene and Parkinson's disease in Chinese subjects

Recent studies have implicated polymorphisms in the 3′ untranslated region (3′UTR) of the alpha-synuclein (SNCA) gene in the development of Parkinson's disease (PD). Single nucleotide polymorphism (SNP) rs356165 is one of polymorphisms located in the 3′UTR and its association with PD has been reported but remains controversial. Herein, we conducted a case-control study to further evaluate the possible association between SNP rs356165 and PD in Chinese. All subjects (330 PD patients and 300 normal controls) were successfully genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. No statistically significant difference in genotype frequency between cases and controls was observed (P = 0.863), suggesting no association of SNP rs356165 with PD in our population. Thus, it may be premature to conclude an association between the 3′UTR of the SNCA gene and PD, and this association should be further examined in different ethnic populations.     

A dopamine D2 receptor gene-related polymorphism is associated with schizophrenia in a Spanish population isolate

Numerous lines of evidence have highlighted the involvement of the dopamine system in the pathophysiology of schizophrenia. Association studies of dopaminergic genes such as the dopamine D2 receptor gene (DRD2), however, have produced contradictory results. To test the hypothesis that DRD2 polymorphisms are associated with schizophrenia, we investigated two DRD2-related polymorphisms (TaqI A1/A2 or rs1800497 and -141-C Ins/Del or rs1799732) in a Spanish population isolate from northern Spain consisting of 165 controls and 119 patients with schizophrenia. The TaqI A1 allele was less frequent in schizophrenic patients than in controls (P=0.002). A similar association was found for the TaqI A2/A2 genotype (P=0.0003). No association was found for the DRD2 -141-C Ins/Del polymorphism. The strong association between a potentially functional polymorphism, downstream of the DRD2 gene and schizophrenia, suggests that the direct or indirect functional effects of this polymorphism, acting on either the ANKK1 or DRD2 genes, may play a role in the pathophysiology of schizophrenia.     

Association between PARK16 and Parkinson's disease in the Han Chinese population: a meta-analysis

PARK16 was reported to alter the risk for Parkinson's disease (PD) in the Japanese population. However, its role in Han Chinese PD patients has not been well established. Herein, we investigated the effect of 4 single-nucleotide polymorphisms (SNPs) within the PARK16 locus, including rs823128, rs947211, rs823156, and rs11240572, on the risk of PD by genotyping 497 Taiwanese patients with PD and 500 age-matched control subjects. The results were then meta-analyzed with available genetic association studies in the same population. The meta-analysis showed that PD patients demonstrated a lower frequency of the rs823128 G allele (11.93%) than control subjects (14.04%; odds ratio [OR] 0.83, 95% confidence interval [CI] 0.72–0.96, p = 0.010). The frequency of the rs947211 A allele (40.35%) in PD patients was lower than in control subjects (43.01%; OR 0.90, 95% CI 0.80–0.99, p = 0.047). The rs823156 G allele was less frequently seen in PD patients (17.32%) than in control subjects (21.35%; OR 0.77, 95% CI 0.69–0.86, p < 0.001). A lower frequency of the rs11240572 A allele was found in PD patients (14.01%) than in control subjects (17.66%; OR 0.76, 95% CI 0.66–0.88, p < 0.001). Our results indicate a robust protective effect of PARK16 in Han Chinese PD patients. Functional approaches are needed to elucidate the effects of these SNPs on the regulation of gene expression.     

Two Rare Variants Explain Association with Acute Myocardial Infarction in an Extended Genomic Region Including the Apolipoprotein(A) Gene

Relatively low numbers of kringle 4 type 2 repeats in apolipoprotein(a) and specific haplotypes of the SLC22A3‐LPAL2‐LPA region on chromosome 6 are associated with an increased risk of coronary disease. We examined the possibility that rs3798220 and rs10455872, short variations located in LPA [the apolipoprotein(a) gene], and related to the number of kringle 4 type 2 repeats, may serve as markers for the association between haplotypes and acute myocardial infarction. Genotypes were determined with TaqMan assays in a sample of 2136 cases and 1211 controls. The minor alleles of rs3798220 and rs10455872 were associated with increased risks (rs3798220‐C: adjusted OR 2.14, 95% CI, 1.37–3.33, P = 0.00080; rs10455872‐G: adjusted OR 1.74, 95% CI 1.36–2.24, P < 0.00001). After adjustments were made for potential confounders, none of nine polymorphisms included in a haplotype analysis were singly related to disease. Two risk haplotypes were identified; one (CCTTGTGTG; OR 1.25, 95% CI 1.08–1.45, P = 0.0022) was correlated with rs3798220‐C and the other (CCCTGGATC; OR 1.65, 95% CI 1.14–2.38, P = 0.0074) with rs10455872‐G. Thus, the findings allowed for a more precise definition of risk‐associated markers: specific nucleotides in LPA instead of standard haplotypes defined by noneffective variants from the extensive SLC22A3‐LPAL2‐LPA region.     

Analysis of single nucleotide polymorphism rs415430 in the <Emphasis Type="Italic">WNT3</Emphasis> gene in Parkinson’s disease in Russian population

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disease that arises as a result of the destruction of dopaminergic neurons. Reasons for the development of PD are not completely clarified and, at present, a number of genes involved in the development of both familial and sporadic PD forms have been detected. According to recent data from genome-wide association studies, single nucleotide polymorphisms (SNPs) in these genes (including the MAPT locus) can play a significant role in the development of PD. In connection with the above, we analyzed the distribution of genotype frequencies of SNP rs415430 in WNT3 gene in Russian patients with sporadic PD and in Russian population controls (OR = 0.84, Confidence Interval (95% CI) 0.58–1.23, p = 0.39). We conclude that the WNT3 gene rs415430 SNP does not influence the risk of the development of PD in the Russian population.     

The maternal 14 bp Ins/Del polymorphism in HLA‐G is not associated with preeclampsia risk

The effect of HLA‐G 14 bp Ins/Del polymorphism (rs371194629) on the risk of preeclampsia has been assessed in several populations, yet the results are still conflicting. Lack of power due to small sample sizes is a common cause of inconsistencies in genetic association studies. We aimed to test whether the maternal polymorphism is associated with preeclampsia, eclampsia or HELLP syndrome (acronym for Hemolysis, Elevation of Liver enzymes, Low Platelets). To achieve a statistical power greater than 0.90, a total of 741 women (332 controls, 246 preeclampsia, 57 eclampsia and 106 HELLP) were genotyped for the 14‐bp Ins/Del polymorphism. The genetic association with disease status was assessed by Fisher's exact test and odds ratio (OR) estimates using logistic regression model adjusted for maternal age and parity status. Allele and genotype distributions were the same between control and case groups (p > .05). The polymorphism was not associated with the risk of developing preeclampsia [OR = 0.93 (0.72–1.19); p = .541], or eclampsia [OR = 0.90 (0.60–1.38); p = .628] nor HELLP syndrome [OR = 0.92 (0.66–1.28); p = .628]. This well‐powered study clearly demonstrates that the maternal HLA‐G 14‐bp Ins/Del polymorphism is not associated with preeclampsia risk. However, as the offspring genotypes were not evaluated here, we could not rule out the effect of the foetal genotype on the preeclampsia pathogenesis.