BACKGROUND: This study aimed to investigate susceptibility to Graves’s disease and the association with the 5q32–33.1 region on chromosome 5 in a Chinese Han population.

MATERIAL AND METHODS: Eighty Chinese Han multiplex families included first-degree and second-degree relatives with Graves’ disease. Eight microsatellite markers on chromosome 5 at the 5q32–33.1 region underwent linkage analysis and the association between the regions D5S1480–D5S2014 were studied.

RESULTS: The maximal heterogeneity logarithm of the odds (HLOD) score of D5S2090 was 4.29 (α=0.42) and of D5S2014 was 4.01 (α=0.34). A nonparametric linkage (NPL) score of 3.14 (P<0.001) was found for D5S2014. The D5S1480–D5S2014 region on chromosome 5 was associated with Graves’ disease, with eight haplotype domains. There were significant differences in the sixth and eighth haplotype domains between patients with Graves’ disease compared with normal individuals. Tagging single nucleotide polymorphisms (SNPs) of the sixth and eighth haplotype domains showed that individuals with SNP62 (rs12653715 G/C) who were GG homozygous had a significantly increased risk of Graves’ disease compared GC heterozygous or CC homozygous individuals. The transmission disequilibrium test (TDT) indicated that SNP62 (rs12653715) and SNP63 (rs12653081) loci in the Janus kinase and microtubule interacting protein 2 (JAKMIP2) gene showed dominant transmission from heterozygous parents to the affected offspring, and SNPs in the secretoglobin family 3A member 2 (SCGB3A2) gene showed no transmission disequilibrium. The haplotype JAKMIP2-1 was identified as being particularly significant.

CONCLUSIONS: JAKMIP2 gene polymorphism require further study as potential risk factors for Graves’ disease in the Chinese Han population.

Keywords: genetic linkage, Graves Disease, Haplotypes, Asians, Case-Control Studies, Chromosomes, Chromosomes, Human, Pair 5, ethnicity, Genetic Predisposition to Disease, Genotype, Homeodomain Proteins, Microsatellite Repeats, Polymorphism, Single Nucleotide, Risk Factors, Tumor Suppressor Proteins