Abstract
BackgroundThis study addresses whether the association of adiponectin gene (ADIPOQ) variants with idiopathic recurrent pregnancy loss (RPL) is influenced by obesity.MethodsRetrospective case–control study performed in outpatient obstetrics/gynecology clinics. Study subjects comprised 308 women with RPL, defined as ≥ 3 consecutive miscarriages of unknown etiology, and 310 control women. ADIPOQ genotyping was done by allele exclusion method on real-time PCR.ResultsOf the 14 ADIPOQ variants tested, the minor allele frequency (MAF) of rs4632532, rs17300539, rs266729, rs182052, rs16861209, and rs7649121 were significantly higher, while rs2241767, and rs1063539 MAF were lower in RPL cases, hence assigning RPL-susceptibility and protection to these variants, respectively. Higher frequencies of heterozygous rs17300539 and rs16861209, and homozygous rs4632532, rs266729, and rs182052 genotypes, and reduced frequencies of heterozygous rs1063539 and rs2241767, homozygous rs2241766 genotypes were seen in RPL cases. ADIPOQ rs4632532, and rs2241766 were associated with RPL in obese, while rs1063539 and rs16861209 were associated with RPL in non-obese women; rs182052 and rs7649121 associated with RPL independently of BMI changes. Based on LD pattern, two haplotype blocks were identified. Within Block 1 containing rs4632532, rs16861194, rs17300539, rs266729, rs182052, rs16861209, rs822396, and rs7649121, increased frequency of CAGGACAT and TAACGAAA, and reduced frequency of TAGCGCAA haplotypes were seen in RPL cases when compared to controls, thereby assigning RPL susceptibility and protection, respectively.ConclusionThis is the first study to document contribution of ADIPOQ variants and haplotypes with RPL, and also to underscore the contribution of obesity to genetic association studies.
Highlights
This study addresses whether the association of adiponectin gene (ADIPOQ) variants with idiopathic recurrent pregnancy loss (RPL) is influenced by obesity
0.94 0.004 0.02 0.69 < 0.001 < 0.001 0.55 < 0.001 0.11 < 0.001 < 0.001 a A total of 308 RPL cases and 310 control women were included b Student’s t-test, Pearson’s χ2 test c Mean ± SD d Percent of total within each group/subgroup included them as covariates which we controlled for in later analysis
Genotype distributions of all 14 tested ADIPOQ variants conformed to Hardy– Weinberg equilibrium (HWE) among study subjects
Summary
This study addresses whether the association of adiponectin gene (ADIPOQ) variants with idiopathic recurrent pregnancy loss (RPL) is influenced by obesity. Modifiable and non-modifiable factors that contribute to RPL pathogenesis were reported The former includes environmental and lifestyle factors (smoking, obesity), Normal human pregnancy is linked with altered metabolism stemming from the accumulation of white adipose tissues [6], leading to progressive decrease in insulin sensitivity [6, 7]. White adipose tissues synthetize an array of hormones within the intra-uterine compartment, which serve both metabolic, anti-atherosclerotic, and Dendana et al J Transl Med (2018) 16:76 anti-inflammatory roles. These include leptin, resistin, apelin, and adiponectin [8]. Adiponectin is a 30 kDa, 244 amino acid adipokine, which regulates insulin sensitivity, blood glucose levels, and lipid metabolism, and possesses anti-atherosclerosis and anti-inflammatory activities [9]
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