Parent-of-origin effects on glucose homeostasis in polycystic ovary syndrome.

Abstract

CONTEXT:

Polycystic ovary syndrome (PCOS) is a highly heritable complex trait. Parents of affected women have reproductive and metabolic phenotypes.

OBJECTIVE:

We tested the hypothesis that there are parental effects on the heritability of fasting dysglycemia in women with PCOS.

DESIGN AND SETTING:

This was a cross-sectional study at an academic medical center.

PARTICIPANTS:

PARTICIPANTS included 367 women with PCOS and their parents (1101 total subjects).

MAIN OUTCOME MEASURES:

We compared maternal and paternal contributions to heritability of fasting dysglycemia and to transmission of the PCOS susceptibility allele of D19S884 within the fibrillin-3 gene (D19S884-A8) on fasting dysglycemia.

RESULTS:

Fathers had higher fasting glucose levels, prevalence of fasting dysglycemia and proinsulin to insulin molar ratios (P < .0001), a marker of defective insulin processing, compared with mothers. Heritability of fasting dysglycemia was significant in PCOS families (h(2) = 37%, SE = 10%, P = .001). Maternal heritability (h(2) = 51%, SE = 15%, P = .0009) was higher than paternal heritability (h(2) = 23 %, SE = 23%, P = .186) of fasting dysglycemia after adjustment for age and body mass index. Within dysglycemic probands, there was increased maternal compared with paternal transmission of D19S884-A8 (maternal 84% vs paternal 45%, χ(2) = 6.51, P = .011).

CONCLUSIONS:

There was a sex difference in the parental metabolic phenotype with fathers having an increased risk of fasting dysglycemia and evidence for pancreatic β-cell dysfunction compared with mothers. However, only maternal heritability had significant effects on the prevalence of fasting dysglycemia in women with PCOS. Furthermore, there were maternal parent-of-origin effects on transmission of D19S884-A8 probands with fasting dysglycemia. These findings suggest that maternal factors, genetic and perhaps epigenetic, contribute to the metabolic phenotype in affected women.

• Authors: Kristen Kobaly, Priyathama Vellanki, Ryan K Sisk, Loren Armstrong, Ji Young Lee, Jungwha Lee, M Geoffrey Hayes, Margrit Urbanek, Richard S Legro, Andrea Dunaif
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 99 Issue 8 Pg. 2961-6 (Aug 2014) ISSN: 1945-7197 [Electronic] United States
• PMID: 24878041 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Blood Glucose

Topics

• Adult
• Blood Glucose (genetics)
• Cross-Sectional Studies
• Fasting (blood)
• Female
• Genetic Predisposition to Disease
• Homeostasis (genetics)
• Humans
• Inheritance Patterns (physiology)
• Male
• Middle Aged
• Phenotype
• Polycystic Ovary Syndrome (blood)
• Quantitative Trait, Heritable
• Young Adult