Low-density lipoprotein receptor-related protein-5 C/T polymorphism in exon 18 is associated with C peptide and proinsulin levels in control women and patients with polycystic ovary syndrome.
OBJECTIVE
To assess the previously unstudied potential role of C/T (A1330V) polymorphism of the low-density lipoprotein receptor-related protein-5 gene in insulin sensitivity and secretion in polycystic ovary syndrome. The low-density lipoprotein receptor-related protein-5 gene has been found to play a role in determining insulin secretion in animal models.


METHODS
Case-control study.


METHODS
Tertiary outpatient clinic.


METHODS
Women with polycystic ovary syndrome (n = 299; age, 27.5 +/- 7.1 y [mean +/- SD]), according to the European Society of Human Reproduction and Embryology criteria, as well as healthy control women (n = 187, age, 28.9 +/- 9.8 y).


METHODS
Oral glucose tolerance test, blood sampling.


METHODS
Glucose, insulin, C peptide, proinsulin during oral glucose tolerance tests, and lipids. Genotyping of C/T (A1330V) polymorphism by polymerase chain reaction-restriction fragment length polymorphism.


RESULTS
There was no difference in the frequency of genotypes between women with polycystic ovary syndrome (CC/CT/TT: 80.3%, 18.4%, 1.3%) and the control women (79.1%, 19.8%, and 1.1%). Carriers of the T allele had statistically significantly higher basal and stimulated C peptide and proinsulin levels than CC homozygotes, both basally and at the 180th minute. Regarding insulin sensitivity, there was no difference between T carriers and CC homozygotes.


CONCLUSIONS
Polymorphism of C/T in the low-density lipoprotein receptor-related protein-5 gene is associated with C-peptide and proinsulin secretion but does not influence insulin sensitivity in either healthy women or women with polycystic ovary syndrome.
Bendlova
Bela
B
Institute of Endocrinology, Charles University, Prague, Czech Republic. bbendlova@endo.cz
Vankova
Marketa
M
Zajickova
Katerina
K
Hill
Martin
M
Zemanova
Adela
A
Cibula
David
D
Vejrazkova
Daniela
D
Lukasova
Petra
P
Vcelak
Josef
J
Vondra
Karel
K
Vrbikova
Jana
J
D000328:Adult; D002096:C-Peptide / Q000097:blood*; D018153:Czech Republic / Q000453:epidemiology; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D011384:Proinsulin / Q000097:blood*; D011973:Receptors, LDL / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors
D002096:C-Peptide; D011973:Receptors, LDL; D011384:Proinsulin