Newborn MTHFR rs1801133 Variant and Extremely Low Birth Weight: A Case-Control Study and Meta-Analysis

Area of Science:

• Genetics
• Neonatology
• Public Health

Background:

• Extremely low birth weight (ELBW) and extremely low gestational age (ELGA) are significant causes of neonatal morbidity and mortality.
• Homocysteine metabolism genes, MTHFR and PON1, are investigated for their role in prematurity complications.

Purpose of the Study:

• To examine the association between functional variants in MTHFR and PON1 genes and the risk of ELGA, ELBW, and other prematurity complications.
• To conduct a meta-analysis integrating current study findings with existing literature data.

Main Methods:

• Genotyping of MTHFR and PON1 variants using TaqMan assays in 377 infants, 164 mothers, and 404 population controls.
• Meta-analysis of five studies (1156 cases, 1124 controls) to confirm associations.

Main Results:

• Fetal MTHFR rs1801133 genotype associated with ELBW (OR=1.65), bronchopulmonary dysplasia, patent ductus arteriosus, and neonatal mortality.
• Meta-analysis confirmed MTHFR genotype association with low birth weight (LBW), specifically the rs1801133T allele in TT homozygotes (OR=1.41).
• Subgroup analyses revealed population-specific effects: protective in developed countries, risk factor in others. No PON1 associations found.

Conclusions:

• Neonatal MTHFR genotype is confirmed to contribute to LBW globally.
• The rs1801133T allele exhibits population-specific protective or risk effects on LBW.
• Findings highlight the importance of considering genetic background in understanding prematurity outcomes.