PMID- 12161510
OWN - NLM
STAT- MEDLINE
DCOM- 20020830
LR  - 20111117
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 87
IP  - 8
DP  - 2002 Aug
TI  - Familial clustering of juvenile thyroid autoimmunity: higher risk is conferred by 
      human leukocyte antigen DR3-DQ2 and thyroid peroxidase antibody status in 
      fathers.
PG  - 3779-82
AB  - Thyroid autoimmunity is one of the most common immune disorders in females, and 
      its polygenic background remains to be elucidated. The human leukocyte antigen 
      (HLA) DQ region of chromosome 6 has been shown to confer susceptibility to 
      thyroid autoimmune disease. The aim of our present investigation was to determine 
      whether the transmission of high risk HLA DQ to patients with thyroid 
      autoimmunity differs when transmission is from fathers as opposed to when 
      transmission is from mothers. We studied 91 juvenile patients with chronic 
      lymphocytic thyroiditis (68 females and 23 males; mean age, 10.5 +/- 3.9 yr), 12 
      patients with Graves' disease (all females; mean age, 8.8 +/- 4.0 yr), 53 healthy 
      siblings, and their parents for thyroid function, antibodies, ultrasound, and DNA 
      typing for HLA DQ susceptibility alleles. We observed an increased rate of 
      transmission for the DQA1*0501-DQB1*0201 (DQ2) haplotype [35 of 53 transmitted 
      (66%); P = 0.02]. This allele was preferentially transmitted by fathers [21 of 27 
      (78%); P < 0.004], whereas the maternal DQ2 haplotypes were not transmitted more 
      often than expected. Subsequently, families were stratified as follows according 
      to the parental thyroid peroxidase antibody (TPOAb) status: no parent, only 
      mothers, only fathers, and both parents positive. There was no significant 
      maternal transmission disequilibrium in any subset, but the paternal HLA DQ2 was 
      preferentially transmitted [11 of 14 cases (79%); P = 0.03] in the group of 
      TPOAb-positive mothers, and we observed a similar trend in the group of TPOAb- 
      positive fathers (P = 0.08). Also, the portion of offspring affected by Graves' 
      disease was significantly higher in TPOAb-positive than in TPOAb-negative fathers 
      (P < 0.02). In conclusion, our findings demonstrate a significant effect of 
      paternal HLA DQ alleles as well as antibody status on susceptibility to thyroid 
      autoimmune disease in juvenile patients.
FAU - Segni, Maria
AU  - Segni M
AD  - Department of Pediatrics, Endocrinology Unit, University La Sapienza, I-00161 
      Rome, Italy.
FAU - Pani, Michael A
AU  - Pani MA
FAU - Pasquino, Anna Maria
AU  - Pasquino AM
FAU - Badenhoop, Klaus
AU  - Badenhoop K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Autoantibodies)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ2 antigen)
RN  - 0 (HLA-DR3 Antigen)
RN  - EC 1.11.1.8 (Iodide Peroxidase)
SB  - IM
MH  - Adolescent
MH  - Alleles
MH  - Autoantibodies/blood
MH  - Birth Order
MH  - Child
MH  - Cluster Analysis
MH  - Family Health
MH  - Fathers
MH  - Female
MH  - Genetic Predisposition to Disease/epidemiology
MH  - HLA-DQ Antigens/*genetics
MH  - HLA-DR3 Antigen/*genetics
MH  - Humans
MH  - Iodide Peroxidase/*immunology
MH  - Male
MH  - Risk Factors
MH  - Seroepidemiologic Studies
MH  - Thyroiditis, Autoimmune/*epidemiology/*genetics/immunology
EDAT- 2002/08/06 10:00
MHDA- 2002/08/31 10:01
CRDT- 2002/08/06 10:00
PHST- 2002/08/06 10:00 [pubmed]
PHST- 2002/08/31 10:01 [medline]
PHST- 2002/08/06 10:00 [entrez]
AID - 10.1210/jcem.87.8.8746 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2002 Aug;87(8):3779-82. doi: 10.1210/jcem.87.8.8746.