Endocrine Abstracts (2006) 11 P693

Association between polymorphisms within the SUR1/Kir6.2 gene region and polycystic ovary syndrome: a case-control study

TM Barber1, E Zeggini2, MJ Goh3, L Webber3, JAH Wass1, S Franks3 & MI McCarthy1


1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom; 2Wellcome Trust for Human Genetics, University of Oxford, Oxford, United Kingdom; 3Institute of Reproductive and Developmental Biology, Imperial College, London, United Kingdom.


Hyperinsulinaemia has an important role in the aetiology of Polycystic Ovary Syndrome (PCOS). Logical candidate genes for the development of PCOS therefore include those genes that influence β-cell insulin secretion such as ABCC8 and KCNJ11 on human chromosome 11. These two genes encode the SUR1 and kir6.2 components of the β-cell kATP channel respectively. To our knowledge, these genes have not been studied in women with PCOS previously.

The objective of these genetic analyses was to establish whether alleles of 6 tag Single Nucleotide Polymorphisms (SNPs) occurring within haplotype block 5 of the SUR1/Kir6.2 gene region are associated with PCOS susceptibility. These tag SNPs are located within the genes ABCC8, KCNJ11 and NUCB2. (The tag SNP, rs5219 responsible for the E23K polymorphism within KCNJ11 is currently being genotyped). A case-control association analysis was performed on a UK population comprising 374 cases and 540 control subjects (all of British/Irish origin). The main outcome measures were genotype frequencies between cases and controls. The Kruskal-Wallis χ2 method was used to test for genotypic associations.

All SNPs were in Hardy-Weinberg equilibrium. There were no significant differences in genotype distributions between the case and control groups, a significant P-value being defined as less than 0.05 (ABCC8 rs2074310, P=0.33; ABCC8 rs2067043, P=0.09; NUCB2 rs1073443, P=0.87; KCNJ11 rs1800467, P=0.86; rs1557764, P=0.05; rs2354867, P=0.06). The distribution of haplotypes in the cases was nominally significantly different from that in the controls (P=0.015). The main haplotype driving this result was CTGGCC which was reduced in frequency in the cases (0.232 versus 0.284 in controls). The proportion of haplotypes captured using the 6 tag SNPs was 96%. These results suggest that polymorphisms within the 6 tag SNPs located within haplotype block 5 of the SUR1/Kir6.2 gene region are not strongly associated with PCOS.

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