Associations of HLA-C alleles with multinodular goiters: study in a population from southeastern Spain.

HYPOTHESIS: Several immunological alterations have been found in patients with multinodular goiter (MG). These alterations, together with the association described between certain autoimmune thyroid diseases and alleles of the major histocompatibility complex (HLA alleles), justify the need for studies of the HLA alleles and MG in an attempt to identify associations.

DESIGN

Case-control study.

SETTING

Tertiary referral center.

PATIENTS: Ninety consecutive patients underwent surgical procedures for MG. The control group comprised 100 unrelated, healthy, white subjects.

INTERVENTION: Genotyping for HLA-C alleles was done using the molecular biological technique of polymerase chain reaction using sequence-specific primers and was carried out for all of the patients.

MAIN OUTCOME MEASURES: The analyzed variables included age, sex, family history of thyroid pathological abnormalities, clinical features of the patient, clinical grading of the goiter, intrathoracic thyroid component, goiter weight, associated carcinoma, and the HLA-C gene.

RESULTS

A significant association was observed between the lower incidence of the HLA-Cw4 allele and the appearance of MG (15.5% vs 8.3%, respectively; P = .001; relative risk [RR] = 0.49). These results suggest that the HLA-Cw4 allele can exert a protective effect against MG. Analysis of the different clinical variables shows the most significant association to be the absence of the HLA-Cw4 allele in patients with goiters with an intrathoracic component (P = .001; RR = 0.19) and in patients with goiters weighing more than 200 g (P = .02; RR = 0.17). Associations between the HLA-C alleles and MG were also observed, such as the presence of the HLA-Cw7 allele and a family history of thyroid pathological abnormalities (P = .03; RR = 3.91) as well as the HLA-Cw1 allele and the presence of goiter-associated thyroid carcinoma (P = .02; RR = 8.60).

CONCLUSIONS

The HLA-Cw4 allele can act as a protector against the development of MG, as it occurs less frequently in the population with MG, and those with this allele develop smaller goiters with no intrathoracic component.