LEPR c.668A&gt;G polymorphism in a cohort of Sri Lankan women with pre-eclampsia / pregnancy induced hypertension: a case control study

Tennekoon, Kamani Hemamala; Indika, Wijesekara Liyanage; Sugathadasa, Rohan; Karunanayake, E.H.; Kumarasiri, J. M.; Wijesundera, Ajita

doi:10.1186/1756-0500-5-308

Cited by 7 publications

(8 citation statements)

References 27 publications

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“…Our finding was in accordance with the findings of Rigo et al in a study of pregnant Hungarian women [18]. However, several other studies showed no association between c.668A>G and preeclampsia [20,21,34,35]. In this study, the frequency of the minor G allele, whether it was the AG or GG genotype, was significantly associated with the development of preeclampsia.…”

Section: Discussionsupporting

confidence: 93%

Leptin receptor gene polymorphisms c.668A>G and c.1968G>C in Sudanese women with preeclampsia: a case-control study

Saad

Adam

Elzaki³

et al. 2020

BMC Med Genet

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Background: Leptin receptor gene (LEPR) variants may affect the leptin levels and act as a risk factor for preeclampsia. Two LEPR gene missense variants rs1137101 (c.668A>G) and rs1805094 (c.1968G>C) were investigated in Sudanese women with preeclampsia. Methods: A matched case-control study (122 women in each arm) was conducted in Saad Abualila Maternity Hospital in Khartoum, Sudan from May to December 2018. The cases were women with preeclampsia and the controls were healthy pregnant women. Genotyping for LEPR gene variants c.668A>G and c.1968G>C was performed using polymerase chain reaction-restriction fragment length polymorphism. Logistic regression models (adjusted for age, parity, body mass index and hemoglobin level) were conducted. Results: Genotype frequency of LEPR gene variants c.668A>G and c.1968G>C was in accordance with Hardy-Weinberg equilibrium (P > 0.05) in the controls. Allele G in LEPRc.668A>G variant was significantly more frequent in the cases compared with the controls [43.4% vs. 10.2%; OR = 6.44; 95%CI (3.98-10.40); P < 0.001]. In variant LEPRc.668A>G, genotype AG was the prevalent genotype in the cases compared with the controls, and it was significantly associated with preeclampsia risk [37.7% vs. 15.5%; AOR = 3.48; 95%CI (1.15-10.54); P = 0.027]. Likewise, the GG genotype was the second most common genotype in the cases compared with the controls, and was associated with preeclampsia risk [24.6% vs. 2.5%; AOR = 14.19; 95%CI (1.77-113.76); P = 0.012]. None of the LEPRc.1968G>C variant genotypes were associated with preeclampsia. The CC genotype was not detected in neither the cases nor the controls. The haplotype A-G 70.1% was the prevalent haplotype in this population, and it significantly protected against preeclampsia [OR = 0.14; 95%CI (0.09-0.23); P < 0.001]. However, the haplotype G-G 26.8% was significantly associated with preeclampsia risk [OR = 6.70; 95%CI (4.16-11.05); P < 0.001]. Both variants c.668A>G and c.1968G>C were in strong linkage disequilibrium (D′ = 1, r 2 = 0.012). Conclusions: Our data indicate that the rs1137101 (c.668A>G) variant and G-G haplotype may independently associate with the development of preeclampsia.

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Section: Discussionsupporting

confidence: 93%

Leptin receptor gene polymorphisms c.668A>G and c.1968G>C in Sudanese women with preeclampsia: a case-control study

Saad

Adam

Elzaki³

et al. 2020

BMC Med Genet

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“…They reported a greater frequency of the R allele for SNPs K109R (c.326A>G, rs1137100) and Q223R (c.668A>G, rs1137101) of the leptin receptor among Asians when compared to Caucasians. In a recent study by our group [37] the frequency of the R allele for Q223R SNP observed among Sri Lankans was within the range of frequencies reported for Caucasians in the meta-analysis. SLR is generated either by alternative splicing of leptin receptor mRNA or by shedding the ectodomain of membrane-bound receptor protein, thus its levels are unlikely to be affected by SNPs of the leptin receptor or their ethnic variations.…”

Section: Discussionmentioning

confidence: 98%

Association of Cord Blood Leptin, Soluble Leptin Receptor, Insulin-Like Growth Factor-I and Insulin-Like Growth Factor-Binding Protein-1 on Birth Indices in Healthy Full-Term Newborns

Tennekoon

Poopalapillai²,

Karunanayake³

et al. 2014

Horm Res Paediatr

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Background: Leptin and insulin-like growth factor-I (IGF-I) promote fetal growth. Their availability is modulated by soluble leptin receptor (SLR) and insulin-like growth factor-binding proteins (IGFBP). Studies that accounted for SLR levels when investigating the association of leptin, IGF-I and IGFBPs on birth indices are scarce. Methods: Cord blood leptin, SLR, IGF-I, IGFBP-1 and their association with birth indices were studied in term newborns (n = 110; males = 60). Data were compared between males and females using the Mann-Whitney U test/unpaired Student's t test as appropriate. Univariate correlations and multiple regression analyses were performed to identify variables significantly influencing birth indices. Results: Birth indices were comparable between male and female newborns. Females had a significantly lower SLR (p = 0.0142), a higher leptin/Ponderal index (p = 0.033) and a higher free leptin index (leptin/SLR) (p = 0.0081). Leptin and male gender positively and IGFBP-1 negatively influenced birth weight (p = 0.0005, p = 0.02, and p = 0.005, respectively) and head circumference (p = 0.0052, p = 0.0098, and p = 0.0183, respectively) when accounted for other variables. When tested in a different multiple regression model, the free leptin index positively influenced crown-heel length (p = 0.0016) in addition to birth weight (p < 0.0001) and head circumference (p = 0.0016). Conclusions: In healthy full-term pregnancies, cord blood leptin and IGFBP-1 exert independent and opposing effects on fetal growth.

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“…Lastly, one can hypothesize that adipokine signaling (more precisely, the AdipoR and ObR adipokine receptors for adiponectin and leptin, respectively) is altered in women with RPL. Indeed, it has already been reported that certain AdipoR and ObR polymorphisms are associated with reproductive traits or certain reproductive pathologies (such as pre‐eclampsia, and hemolysis, elevated liver enzyme levels and low platelet levels syndrome) …”

Section: Discussionmentioning

confidence: 99%

Are leptin and adiponectin involved in recurrent pregnancy loss?

Sérazin

Duval

Wainer

et al. 2018

J of Obstet and Gynaecol

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LEPR c.668A>G polymorphism in a cohort of Sri Lankan women with pre-eclampsia / pregnancy induced hypertension: a case control study

Cited by 7 publications

References 27 publications

Leptin receptor gene polymorphisms c.668A>G and c.1968G>C in Sudanese women with preeclampsia: a case-control study

Leptin receptor gene polymorphisms c.668A>G and c.1968G>C in Sudanese women with preeclampsia: a case-control study

Association of Cord Blood Leptin, Soluble Leptin Receptor, Insulin-Like Growth Factor-I and Insulin-Like Growth Factor-Binding Protein-1 on Birth Indices in Healthy Full-Term Newborns

Are leptin and adiponectin involved in recurrent pregnancy loss?

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