Infertility in Saudi Women Linked to Polymorphism in the Paraoxonase 1 Gene

There is an association between Q192R polymorphism in the paraoxonase 1 (PON1) gene and female infertility in Saudi women, according to the results of a case-controlled study published in the Journal of King Saud University – Science. The research also suggested obesity may be linked to female infertility.

Infertility is reported to be one of the most common chronic health conditions and affects 15% of all couples worldwide, with female infertility accounting for 40% of all cases, according to one prior study on female infertility.

"Many causes of female infertility have been identified, with the majority of them being genetic abnormalities such as chromosomal defects or single gene mutations," the researchers noted.

This study included a total of 222 Saudi women, in which 122 were infertile and 100 were fertile. Cases of infertility were included if the woman had a history of infertility in her family and had also been trying to conceive for more than 2 to 3 years. Women with a regular menstrual cycle and ability to conceive without a family history of infertility were included in the fertile women control group.

Genomic DNA was extracted from all participants, and underwent a variety of tests, including quantified performed polymerase chain reaction, agarose gel run, and restriction fragment length polymorphism (RFLP) analysis.

According to the results, Q129R polymorphism confirms the allele (P = .003) and genetic association (QR v QQ; P = .001) with different modes of inheritances, including dominant and co-dominant models (P = .003). Furthermore, the researchers found an association between weight and Q192R polymorphism (P = .04), suggesting obesity may also be linked to female infertility.

Additional demographic data collected included the participant’s age, height, weight, and body mass index (BMI). Although the mean age between fertile (28.3±6.8) and infertile (32.7±5.9) women was not statistically significant (P = .0001), the researchers were able to identify a variation between weight (P = .006) and BMI in both groups (31.4±4.3) and in the controls (28.8±4.4; P = .00001). Weight was associated with elevated QQ genotypes (80.6±12.3) among 3 models of genotyping when compared with QR (78.4±12.6) and RR (71.8±10.8) genotypes.

In the fertile group, genotyping distribution was QQ (69%), QR (22%), and RR (9%). In the infertile group, it was QQ (47.5%), QR (40.2%), and RR (12.3%). Additionally, the Q allele was 80% more common than the R allele (20%) in the fertile group, whereas in the infertile group, the R allele was 70% more common than the Q allele (68%). Furthermore, when comparing groups, allele frequency was found to be associated with infertility (odds ratio [OR], 1.91; 95% CI, 1.23-2.96; P = .003). When compared to the homozygous QQ genotype, the Heterozygous genotype was associated with infertility (QR v QQ; OR, 2.65; 95% CI, 1.43-4.88; P = .001). Additionally, there was also an association between co-dominant models (OR, 1.41; 95% CI, 1.31-4.31; P = .003).

The results of this study align with prior studies that found a high variability in PON1 enzymes may be linked with various health issues, such as pregnancy loss and female infertility. The researchers recommend further studies in order to evaluate the potential genetic risk factors of interactions with additional PON1 polymorphisms.

“This study concludes as Q192R polymorphism was positively associated in this case-control study performed in the Saudi women diagnosed with female infertility,” wrote the researchers. “However, obesity factor might also be playing a role in the infertile women.”

Reference

Alshammary AF. Genetic association between Q192R polymorphism in the paraoxonase 1 gene and female infertility in the Saudi women: Validated using DNA sequencing analysis. Journal of King Saud University - Science. 2023;35(3):102567. doi:10.1016/j.jksus.2023.102567