Possible Gene-Gene Interaction of KIR2DL4 With its Cognate Ligand HLA-G in Modulating Risk for Preeclampsia

Tan, Chia Yee; Chong, Yap Seng; Loganath, A.; Chan, Yiong Huak; Jeganathan, Ravichandran; Lee, Caroline; Chong, Samuel S.

doi:10.1177/1933719109342280

Cited by 19 publications

(15 citation statements)

References 53 publications

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“…Although it is very unlikely that this amino acid substitution changes the overall conformation of HLA-G, it has been recently suggested that this allele could modulate the interaction of HLA-G molecules with the KIR2DL4 receptor on NK cells. 20 Nevertheless, the authors cannot exclude the possibility that the associations found between HLA-G alleles and invasive cancer risk may be the result of linkage disequilibrium with other unknown functional loci. The 3 0 UTR 14-bp polymorphism has been associated with the magnitude of HLA-G production, particularly by modulating HLA-G mRNA stability.…”

Section: Discussionmentioning

confidence: 96%

Human leukocyte antigen G polymorphism is associated with an increased risk of invasive cancer of the uterine cervix

Ferguson

Ramanakumar

Koushik

et al. 2012

Intl Journal of Cancer

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Human leukocyte antigen (HLA)-G acts as negative regulator of the immune responses and its expression in tumor cells may enable them to escape immunosurveillance. The purpose of this study was to investigate the influence of HLA-G polymorphism on risk of high-grade cervical intraepithelial neoplasia (HG-CIN) and cervical cancer in a Canadian population. The authors have analyzed 1,372 women from participants recruited between 2001 and 2009 in the ongoing Biomarkers of Cervical Cancer Risk case-control study. A total of 539 women with histologically confirmed HG-CIN and invasive cancer formed the case series, and 833 women with normal cytology served as controls. Cervical specimens were tested for human papillomavirus (HPV) DNA using the MY09/11 PCR protocol and HLA-G alleles where determined using a direct DNA sequencing procedures. HLA-G polymorphisms were not associated with HG-CIN or HPV infection. However, the risk for invasive cancer was significantly increased with the homozygous genotypes HLA-G*01:01:02 [odds ratio (OR) 5 3.52, 95% confidence interval (CI): 1.43-8.61, p 5 0.006], 2G*01:06 (OR 5 19.1, 95% CI: 2.29-159, p 5 0.005) and 2G* 3 0 UTR 14-bp insertion (OR 5 2.17, 95% CI: 1.10-4.27, p 5 0.020), whereas, the heterozygotic form of the G*01:01:01 wild-type allele was significantly associated with a reduced risk of invasive cancer (OR 5 0.31, 95% CI: 0.16-0.59, p < 0.0001) after adjusting for age, HPV infection and ethnicity. These associations were also observed with progression of disease from HG-CIN to invasive cancer among HPV-positive women. These results suggest that HLA-G polymorphism is an independent risk factor for the development of invasive cervical cancer.

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Section: Discussionmentioning

confidence: 96%

Human leukocyte antigen G polymorphism is associated with an increased risk of invasive cancer of the uterine cervix

Ferguson

Ramanakumar

Koushik

et al. 2012

Intl Journal of Cancer

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“…A familial predisposition to PE has been documented, and both men and women who were the offspring of a pregnancy complicated by PE are significantly more likely to have a pregnancy complicated by PE (Esplin et al, 2001). Although a genetic susceptibility to PE has been established with both maternal and fetal genes and a number of association studies have been performed, the results are inconsistent, and the causative genes involved in PE have yet to be identified (He et al, 2009;Tan et al, 2009).…”

Section: Introductionmentioning

confidence: 87%

Meta analysis of angiotensin-converting enzyme I/D polymorphism as a risk factor for preeclampsia in Chinese women

Zhong

Wang²,

Hong³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. Preeclampsia affects 3-8% of pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. Inappropriate activation of the renin-angiotensin system may play a role in the development of preeclampsia. An insertion/ deletion polymorphism in the angiotensin-converting enzyme gene (ACE-I/D) has been associated with differences in ACE activity. However, there are controversies in reports on the association of ACE-I/D with preeclampsia. Data were analyzed using Review Manager Version 5.0 and a random effects model was applied irrespective of between studies heterogeneity, which was evaluated via sensitivity and subgroup analyses. Publication bias was evaluated using the fail-safe number. A systematic search was performed based on published case control studies up to October 1, 2011, and 11 studies were included, involving 800 patients and 949 controls. Significant association of the ACE D allele with increase risk of preeclampsia was found (odds ratio = 1.93, 95% confidence interval = 1.19-3.12; P = 0.008). Sensitivity analysis showed that no individual study had an undue influence on the ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (3): 2268-2276 (2012) Angiotensin-converting enzyme polymorphism and preeclampsia 2269 summary odds ratios for all contrasts. An analysis stratified by study size showed an attenuated odds ratio towards a null effect as study size increased. Based on our meta-analysis, we suggest that the D allele of the ACE gene is related with increased risk for preeclampsia in the Chinese population. Considering the potential existence of small study bias, further research should be performed with a larger dataset.

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“…However, simultaneous activation of the activating isoform of KIR on NK cells can prevent the inhibition of NK cells and mediate proper trophoblast invasion [18]. Pregnant women with fetus carrying the +14/+14 HLA-G genotype or gene-to-gene interaction between fetal HLA-G and maternal KIR2DL4 in multigravid pregnancy may predispose women to PE [19, 20]. Endoplasmic reticulum aminopeptidase 2 (ERAP2) regulates blood pressure (BP) and cytokine production in Norm-Preg.…”

Section: Introductionmentioning

confidence: 99%

Bioactive factors in uteroplacental and systemic circulation link placental ischemia to generalized vascular dysfunction in hypertensive pregnancy and preeclampsia

Shah

Khalil

2015

Biochemical Pharmacology

151

124

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Preeclampsia is a pregnancy-associated disorder characterized by hypertension, and could lead to maternal and fetal morbidity and mortality; however, the pathophysiological mechanisms involved are unclear. Predisposing demographic, genetic and environmental risk factors could cause localized abnormalities in uteroplacental cytoactive factors such as integrins, matrix metalloproteinases, cytokines and major histocompatibility complex molecules leading to decreased vascular remodeling, uteroplacental vasoconstriction, trophoblast cells apoptosis, and abnormal development of the placenta. Defective placentation and decreased trophoblast invasion of the myometrium cause reduction in uteroplacental perfusion pressure (RUPP) and placental ischemia/hypoxia, an important event in preeclampsia. RUPP could stimulate the release of circulating bioactive factors such as the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin that cause imbalance with the pro-angiogenic factors vascular endothelial growth factor and placental growth factor, or cause the release of inflammatory cytokines, reactive oxygen species, hypoxia-induced factor-1 and AT1 angiotensin receptor agonistic autoantibodies. The circulating bioactive factors target endothelial cells causing generalized endotheliosis, endothelial dysfunction, decreased vasodilators such as nitric oxide and prostacyclin and increased vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction. The bioactive factors also stimulate the mechanisms of VSM contraction including Ca2+, protein kinase C, and Rho-kinase and induce extracellular matrix remodeling leading to further vasoconstriction and hypertension. While therapeutic options are currently limited, understanding the underlying mechanisms could help design new interventions for management of preeclampsia.

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Possible Gene-Gene Interaction of KIR2DL4 With its Cognate Ligand HLA-G in Modulating Risk for Preeclampsia

Cited by 19 publications

References 53 publications

Human leukocyte antigen G polymorphism is associated with an increased risk of invasive cancer of the uterine cervix

Human leukocyte antigen G polymorphism is associated with an increased risk of invasive cancer of the uterine cervix

Meta analysis of angiotensin-converting enzyme I/D polymorphism as a risk factor for preeclampsia in Chinese women

Bioactive factors in uteroplacental and systemic circulation link placental ischemia to generalized vascular dysfunction in hypertensive pregnancy and preeclampsia

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