P–703 Association of DENND1A and THADA gene variants with polycystic ovary syndrome in women of Arab ethnicity
Authors: Al-Khaduri M , Kindi F. A , Farsi Y. A 
Published: August 2021

Study question

Are THADA and DENND1A gene variants associated with PCOS in Arab populations suggesting that they are likely to be important in the etiology of PCOS regardless of ethnicity.

Summary answer

All SNPs in DENND1A and THADA found in PCOS cases and controls in our study are different from those reported from other ethnicities.

What is known already

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with environmental and genetic factors contributing to its etiology. PCOS is the commonest cause of female infertility and is associated with type2 diabetes mellitus and cardiovascular disease. Genome-wide association study (GWAS) of PCOS in Chinese women identified reproducible PCOS susceptibility loci mapping to LHCGR, THADA, and DENNDIA. THADA and DENND1A were reported to be associated with PCOS in European populations suggesting that they are likely to be important in the etiology of PCOS regardless of ethnicity. However the impact of these loci on PCOS in other ethnicities remains to be determined.

Study design, size, duration

A sample size of 49 cases and 49 controls was estimated for a significance level of 5% at 60% power, with minor allele frequencies of 12% and 1% in cases and controls respectively with a 1:1 ratio. We conducted a prospective study on 50 PCOS cases and 50 control Omani females from the Gynecology clinic at the Sultan Qaboos University Hospital, a tertiary care hospital in Oman from 2019 to 2020. Participants/materials, setting, methods: Cases fulfilled the Rotterdam criteria for PCOS. Patients with genetic disorders, congenital adrenal hyperplasia, androgen secreting tumors, Cushing syndrome, and hyperprolactinemia were excluded from this study. Data collected included history, physical examination and laboratory test results. Gene Panel Exome Sequencing was conducted on DNA extracted from blood samples for THADA and DENND1A and data analyzed using ANNOVAR software. Statistical analysis was performed using SPSS for Descriptive statistics, Chi square test and Correlation analysis.

Main results and the role of chance

The highest frequency variants in DENND1A gene among Omani women were: rs2491348, rs2808409, rs2797946, rs2808411 and rs10739633. The highest frequency variants in THADA were: rs11900952, rs4337518, rs1158411, rs11893207 and rs13021894. All SNPs in DENND1A and THADA found in PCOS cases and controls in our study are different from those reported from other ethnicities. There was a significant association of DENND1A rs2808411 with Hirsutism and high TSH (p value ≤ 0.05). For THADA there was a mild negative correlation between TSH levels and the occurrence of rs33979934 among PCOS cases (p value ≤ 0.05). No significant relationship was found between other hormonal parameters and the occurrence of other selected THADA variants among cases. There was a mild negative correlation between High Density lipoprotein (HDL), total Cholesterol levels and the occurrence of rs33979934 among PCOS cases (p value ≤ 0.05). No significant relationship was found between hormonal or biochemical parameters and the occurrence of variants among the controls.

Limitations, reasons for caution

The limitation of this study were the small sample size and that the study was conducted in a single center.

Wider implications of the findings: Further analysis is needed to establish a cause-and-effect relationship between THADA, DENND1A genes and PCOS among women of Arab ethnicity.

Trial registration number

IG/MED/OBGY/19/01