Vitamin D Deficiency With Selected Vitamin D Receptor Gene Polymorphism in Gestational Hypertension

Association of Vitamin D Deficiency With Selected Vitamin D Receptor (VDR) Gene Polymorphism in Gestational Hypertension Among Malaysian Women: A Prospective Genetic Biomarker for Early Intervention Strategy

This study aim to look into the prevalence of Vitamin D deficiency among Malaysian pregnant women and its associated risk factors. Subsequently, vitamin D deficient women with and without gestational hypertension will be investigated for their genetic variation to look for the association of VDR genetic variation and hypertensive disorders in pregnancy.

Study Overview

• Status: Active, not recruiting
• Conditions: Vitamin D Deficiency; Hypertensive Disorder of Pregnancy
• Intervention / Treatment: Diagnostic test: Blood taking

Detailed Description

Hypertensive disorders of pregnancy account for approximately 14% of maternal mortality globally and is the fourth leading cause of maternal mortality in Malaysia. Despite this, the mechanisms and pathogenesis are still unknown. Vitamin D deficiency (hypovitaminosis vitamin D) has been shown to be one of the causes of gestational hypertension(GH).

Several populations have observed the association of single nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) to vitamin D deficiency among pregnancy complications, including GH. Alarming cases of hypovitaminosis D in sunny areas including Malaysia, highly imply the need to understand the genetic factor. Hence, genotyping VDR variants among pregnant women is essential for early vitamin D supplementation strategy. To investigators knowledge, there has been no published study conducted among Malaysian population on the association of VDR genetic variation and GH. Therefore, this study aim to investigate the prevalence of vitamin D deficiency and its association of VDR SNPs to the development of GH among Malaysian pregnant mothers, with the main focus on Malays, representing the largest ethnic in Malaysia.

The prevalence will be determined through a cross-sectional study involving 363 pregnant women recruited in Hospital Pengajar UPM (HPUPM) and Hospital Serdang, Selangor. Relevant socio-demographic, clinical and anthropometric data will be collected using structured interviewer-administered questionnaire. Blood specimens for the analysis of vitamin D will be done. The association will be determined in a case-control study involving 180 pregnant women who fulfilled the criteria, recruited from phase 1 study. Their blood will be further analysed for the variants of the VDR gene [(BsmI(rs1544410), FokI(rs2228570), TaqI(rs731236)] to look for the association.

This study expected to provide more evidence for early personalised intervention of vitamin D supplementation due to anticipated individual genetic variability. This antenatal care programme will reduce the government expenditures, reduce maternal and fetal morbidity and mortality while strengthening Malaysia's healthcare system.

• Study Type: Observational
• Enrollment (Estimated): 180

Contacts and Locations

Study Locations

• Malaysia
  • Selangor Darul Ehsan
    • Serdang, Selangor Darul Ehsan, Malaysia, 43400
      • Hospital Pengajar UPM

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 46 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

All Malaysia pregnant women attending Obstetrics and Gynaecology Department of Hospital Pengajar UPM(HPUPM) and Hospital Serdang who fulfilled the criteria will be recruited.

Description

Inclusion Criteria:

1. Malay pregnant women with gestational age between 20 weeks till 42 weeks. (The gestational age will be determined from the first day of the last menstrual cycle or measurement of fetal crown rump length)
2. Malay pregnant women with viable pregnancy with or without pregnancy induced hypertension or its complications (pre-eclampsia, eclampsia, HELLP syndrome etc).
3. Literate in either English or Malay languages.
4. Agreement to follow-up till delivery and provision of written informed consent.

Exclusion Criteria:

1. Non-viable pregnancy at the time of recruitment.
2. Women already on vitamin D supplements or any other drugs that can interfere with vitamin D absorption or metabolism at the time of recruitment.
3. Women with chronic hypertension diagnosed prior to pregnancy.
4. Pregnant women with any other chronic disease that is known to affect vitamin D such as, autoimmune disease and any malignancy

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1- normotensive women; Women with vitamin D deficiency and normotensive during pregnancy	Diagnostic test: Blood taking; Blood test for vitamin D level and DNA extraction for VDR gene polymorphism
2- women with hypertensive disorder in pregnancy; Women with Vitamin D deficiency and hypertensive disorder in pregnancy	Diagnostic test: Blood taking; Blood test for vitamin D level and DNA extraction for VDR gene polymorphism

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of vitamin D deficiency	To determine the prevalence of Vitamin D deficiency among Malaysian pregnant mothers	1 year
Risk factors of vitamin D deficiency	To determine the associated risk factors of vitamin D deficiency among Malaysian pregnant mothers-weight, height and BMI will be measured in kg/m2.	1 year
Risk factors of vitamin D deficiency	To determine the associated risk factors of vitamin D deficiency among Malaysian pregnant mothers-duration of sun exposure in a week, measured in hours	1 year
Risk factors of vitamin D deficiency	To determine the associated risk factors of vitamin D deficiency among Malaysian pregnant mothers-intake of food rich in vitamin D, measured in serving number per week	1 year
VDR allele and genotype	To understand and associate distributions of VDR allele and genotype with vitamin D deficiency among Malay pregnant mothers	1 year
VDR-combined genotypes and gestational hypertension	To associate VDR-combined genotypes with the risk to develop gestational hypertension in vitamin D deficient Malay pregnant women	6 months

Collaborators and Investigators

• Sponsor: Universiti Putra Malaysia
• Collaborators: Ministry of Higher Education, Malaysia
• Investigators: Principal Investigator: Nurul I Basri, MbChb, Universiti Putra Malaysia

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Estimated): July 30, 2025
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: November 6, 2022
• First Submitted That Met QC Criteria: December 17, 2022
• First Posted (Actual): December 21, 2022

Study Record Updates

• Last Update Posted (Actual): June 12, 2025
• Last Update Submitted That Met QC Criteria: June 9, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Nutrition Disorders; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Infections; Avitaminosis; Deficiency Diseases; Malnutrition; Hypertension, Pregnancy-Induced; Hypertension; Vitamin D Deficiency; Toxemia
• Other Study ID Numbers: FRGS/1/2022/SKK01/UPM/02/1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No