title: Genetic association of adipokine and UCP2 polymorphism with recurrent miscarriage among non-obese women.
abstract: The adipokines produced from adipose tissues influence energy homeostasis, resulting in alterations of the adipokine concentrations. This process may be associated with fertility impairment, resulting in recurrent miscarriage. The present study investigated whether there was any association between the UCP2 45-bp indel polymorphism and the adipokine gene polymorphisms, namely leptin 2549 (C/A), adeponectin 276 (G/T) and 45 (T/G) and resistin 420 (C/G) in 200 non-obese recurrent miscarriage patients and 300 ethnically matched negative controls. These markers were studied using gene-specific PCR single specific primer and restriction fragment length polymorphism. For leptin 2549 and adeponectin 276, the A allele and G allele showed 3.42-fold (P=0.0001) and 1.36-fold (P=0.036) increased risk of recurrent miscarriage, respectively. Combined analysis of UCP2 45-bp indel and leptin 2549 showed U0-L0 and U1-L0 variants to be at 2- and 3-fold increased associative risk, respectively. Combined analysis of leptin 2549 and adeponectin 276 showed L0-D0 and L0-D1 variants to be at 2- and 4-fold increased associative risk, respectively. The combination U1-L0-D1-A1-R1 was 4.39-fold higher (P=0.0007) among recurrent miscarriage patients. In conclusion, the results highlight the role of the studied adipokine and UCP2 polymorphisms in recurrent miscarriage among the North Indian non-obese population. Pregnancy invokes a large shift in maternal metabolism. The normal concentrations of adipokines, which maintain the integrity of the hypothalamus-pituitary-gonadal axis, regular ovulatory processes and successful embryo implantation, are altered because of the influence of energy homeostasis, which in turn leads to fertility impairment and recurrent miscarriage of unknown aetiology. Recurrent miscarriage is reported in higher frequency among obese women. The UCP2 45-bp indel polymorphism and the adipokine gene polymorphisms namely leptin 2549 (C/A), adeponectin 276 (G/T), adeponectin 45 (T/G) and resistin 420 (C/G) have been shown to be associated with obesity. Most of the adipokine-related studies done previously have taken into consideration the metabolic function and obesity. However, there exist very few studies to evaluate the role of adipokines in non-obese recurrent miscarriage with no cause of repeated pregnancy losses. The present study focused at evaluating the independent effect of these single-nucleotide polymorphisms in non-obese women undergoing recurrent miscarriage.
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India.
authors.forename: Prashant Kumar
authors.initials: PK
authors.lastname: Verma
authors.forename: Swayam
authors.initials: S
authors.lastname: Prakash
authors.forename: Farah
authors.initials: F
authors.lastname: Parveen
authors.forename: Rehan Mujeeb
authors.initials: RM
authors.lastname: Faridi
authors.forename: Suraksha
authors.initials: S
authors.lastname: Agrawal
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D054392:Adipokines / Q000235:genetics*; D000328:Adult; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D020738:Leptin / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics*; D009765:Obesity / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D052243:Resistin / Q000235:genetics; D012307:Risk Factors; D000071246:Uncoupling Protein 2
chemical_list: D054392:Adipokines; D005819:Genetic Markers; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; D052243:Resistin; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2