Association of single nucleotide polymorphism of uric acid transporter gene, SLC2A9 rs1014290, with early onset pre-eclampsia in Indian population

Pre-eclamplsia is a hypertensive complication of pregnancy with serious maternal and perinatal morbidity. It is estimated to affect 45% of pregnancies worldwide.   It can be classified based on the severity into mild and severe type, with mild pre-eclampsia being characterized by blood pressure greater than 140/90 but less than 160/110 mmHg, proteinuria less than 300 mg but not more than 2.0 g in 24-hour urine sample and severe pre-eclampsia being characterized by blood pressure greater than 160/110mmHg, urinary protein concentration more than 2.0 g in 24-hour urine sample. Pre-eclampsia can also be classified as early and late onset type depending on whether the condition was diagnosed before or after 33weeks+6days of gestation.

Early onset pre-eclampsia (EOPE) was associated with more severe maternal cardiovascular, respiratory, renal morbidity when compared with that of late onset pre-eclampsia(LOPE).EOPE was also associated with SGA(short for gestational age) and high neonatal complications and neonatal mortality.

Uric acid plays a pivotal role in free radical scavenging, acting as both pro‐oxidant and antioxidant. Raised uric acid level has also been associated with up-regulation of NLRP3 (Nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome which eventually leads to production of inflammatory markers and ROS(Reactive Oxygen Species) leading to placental pyroptosis which again has been implicated in development of pre-eclampsia. Studies have indicated that in pre-eclamptic group concentrations of caspase-1, IL-1β, TNF-α and HMGB1 were significantly higher but levels of IL-18 were reduced. Single Nucleotide Polymorphisms (SNPs) can lead to differential uric acid excretion by altering the functions of urate transporters.  SLC2A9 encodes glucose transporter 9 (GLUT9), which act as a facilitative transporter of glucose, fructose and uric acid. A study conducted in African population concluded that there was significant association of SLC2A9 (rs1014290)  with early onset preeclampsia. The objective of the study is to find whether there is an  association between Single Nucleotide polymorphisms rs1014290 of SLC2A9 gene with pre-eclampsia in Indian population.