Phosphodiesterase 8B Polymorphism rs4704397 Is Associated with Infertility in Subclinical Hypothyroid Females: A Case-Control Study

Background: Subclinical hypothyroidism (SCH) remains largely unnoticed as a major cause of infertility due toasymptomatic. Polymorphisms of phosphodiesterase 8B gene (PDE8B) have been linked with various diseases,including female infertility. Hence, we aimed to study prevalence of SCH, in infertile females, explore associationof PDE8B rs4704397 A/G and rs6885099 G/A polymorphisms with infertility in females suffering fromSCH and genotype-phenotype correlation of the polymorphisms with thyroid stimulating hormone (TSH) levelsin Gujarat population.Materials and Methods: In this retrospective study, TSH level was estimated from plasma of 230 infertile and100 control females by enzyme-linked fluorescence immunoassay (ELFA) to find out the prevalence of SCH.Further, based on TSH levels, thyroid function test (TFT) was performed in controls and infertile females withsubclinical hypothyroidism (IF-SCH). PDE8B rs4704397 and rs6885099 polymorphisms were genotyped byPCR-RFLP and ARMS-PCR, respectively in 74 controls and 60 IF-SCH females.Results: We observed i. significantly high prevalence of SCH (32%) in the infertile females, ii. significantlylower frequency of ‘G’ allele (P=0.006), while the frequency of ‘A’ allele (P<0.0001) was higher in IFSCHfemales, compared to the controls, for rs4704397 A/G SNP, iii. no significant difference in the genotype(P=0.214; OR=2.51; CI=0.74–8.42) and the allele frequency (P=0.129; OR=1.51; CI=0.92-2.47) of rs6885099G/A SNP, iv) low linkage disequilibrium for the polymorphisms, v. significantly higher frequency of ‘AA’ haplotype(P=0.0001; OR=3.84; CI=1.86-8.01),while the ‘GG’ haplotype (P=0.0023; OR=0.33; CI=0.16-0.69) wassignificantly lower in IF-SCH females and vi. no significant difference in the TSH level of IF-SCH females withrespect to the genotypes.Conclusion: The present study reports an association of PDE8B rs4704397 polymorphism with infertility inSCH females. The study categorically shows a higher prevalence of SCH in infertile females of Gujarat andadvocates the importance of screening for SCH in infertility management.