Genetic regulation of immunoglobulin and specific antibody levels in twins reared apart.

Kohler, P F; Rivera, Víctor; Eckert, Elke D.; Bouchard, Thomas J.; Heston, Leonard L.

doi:10.1172/jci111787

Cited by 29 publications

(15 citation statements)

References 12 publications

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“…6 Multitudinous environmental factors including infections, smoking and chemical compounds can contribute to this variation. [7][8][9] Reports of pedigree studies or twin studies 10,11 have shown that genetic factors are more important than environmental exposures in determining serum immunoglobulin level in human. 12,13 The values of genetic heritability was h 2 ¼ 0.617 þ 0.020 for IgG.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese male population

Liao

Zhang

et al. 2012

Genes Immun

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IgG has a crucial role in humoral immune response. Serum IgG level is mainly determined under genetic control. To explore the genetic influence on serum IgG levels, a two-stage genome-wide association study (GWAS) was performed in a healthy Chinese population of 3495 men, including 1999 unrelated subjects in the first stage and 1496 independent individuals in the second stage. Three single-nucleotide polymorphisms (SNPs) located in TNFRSF13B on 17p11.2 or nearby were significantly associated with IgG level: rs4792800 in the intron (combined P-value ¼ 1.45 Â 10 À 12 ), rs12603708 in the intron (combined P-value ¼ 1.82 Â 10 À 8 ) and rs3751987 at B65 kb downstream of the 5 0 -UTR region of TNFRSF13B (combined P-value ¼ 3.67 Â 10 À 9 ). Additionally, smoking was identified to be associated with IgG level in both stages (Po0.001), but there was no significant interaction between smoking and the identified SNPs (P40.05). The strong association between variants at TNFRSF13B and IgG level may be helpful to further explore the biological mechanism by which the serum IgG is affected by transmembrane activator, calcium modulator and cyclophilin ligand interactor encoded by TNFRSF13B.Genes and Immunity (2012) 13, 509-513; doi:10.1038/gene.2012.26; published online 7 June 2012Keywords: IgG; genome-wide association studies; TNFRSF13B; TACI; smoking INTRODUCTION IgG, constituting some 80% of total serum immunoglobulin, is the most abundant class of antibodies (Ab) in serum and extracellular fluid. It has an important role in the defense against various pathogens, toxins and even cancers. 1 As the only isotype that can pass through the human placenta, IgG is able to protect the fetus in utero. 2 Meanwhile, IgG gets involved in chronic inflammatory processes contributed to the destruction of healthy tissues in autoimmune diseases, such as arthritis and systemic lupus erythematosus. 3 Serum IgG level varies considerably from one person to another, 4 but little when testing the same person repeatedly. 5 This variation in the serum IgG concentration reflects the balance among the rates of synthesis and catabolism. 6 Multitudinous environmental factors including infections, smoking and chemical compounds can contribute to this variation. 7-9 Reports of pedigree studies or twin studies 10,11 have shown that genetic factors are more important than environmental exposures in determining serum immunoglobulin level in human. 12,13 The values of genetic heritability was h 2 ¼ 0.617 þ 0.020 for IgG. 6 Besides, several studies in a population of common variable immunodeficiency patients or IgA deficiency patients implied that there might be an association between some gene loci and serum IgG level. 14,15 However, to the best of our knowledge, no study has ever been conducted to identify the immune loci directly involved in the regulation of the IgG level.Genome-wide association study (GWAS) is a powerful and unbiased tool for the identification of common genetic variants associated with complex traits. 16 This hypothesis-free approach base...

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Section: Introductionmentioning

confidence: 99%

Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese male population

Liao

Zhang

et al. 2012

Genes Immun

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“…Families share environmental as well as genetic factors. In a comparison of monozygotic and dizygotic twin pairs, genetic rather than environmental factors were found to control levels of immunoglobulin and specific antibodies to tetanus toxoid or pneumococcal polysaccharide [40]. However, the nature of these genetic factors differs for different antibody responses.…”

Section: Discussionmentioning

confidence: 95%

Thyroid peroxidase autoantibody epitopic ‘fingerprints’ in juvenile Hashimoto’s thyroiditis: evidence for conservation over time and in families

Jaume

Burek

Hoffman

et al. 1996

Clinical and Experimental Immunology

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SUMMARYIn Hashimoto's thyroiditis, the humoral component is manifest by autoantibodies to thyroid peroxidase (TPO). Epitopic 'fingerprinting' of polyclonal serum TPO autoantibodies has been facilitated by the molecular cloning and expression as Fab of a repertoire of human TPO autoantibody genes. To investigate whether TPO autoantibody fingerprints are (i) stable over long periods of time ( 15 years), and (ii) inherited, we studied a cohort of nine patients with juvenile Hashimoto's thyroiditis and 21 first degree relatives of four of these patients. Fingerprints were determined by competition between four selected Fab and serum autoantibodies for binding to 125 I-TPO. Regardless of titre, the TPO epitopic profile was stable in 10/12 individuals whose TPO autoantibody levels were sufficient for analysis on two or three occasions over 12-15 years. Although the TPO epitopic fingerprint profiles in two families raised the possibility of inheritance, overall the data from all four families did not reveal an obvious pattern of genetic control. In no family was the TPO epitopic fingerprint associated with HLA A, B or DR. In conclusion, TPO autoantibody epitopic fingerprints are frequently conserved over many years. Studies on additional families are necessary to establish whether or not the epitopic profiles of TPO autoantibodies are inherited.

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“…In general, humoral immune responses to specific antigens are influenced to variable degrees by environmental and genetic factors [Allansmith et al, 1969;Klaff and Hijmans, 1969;Kohler et al, 1985;Dunlap et al, 1993;Konradsen et al, 1993]. Twin studies in West Africa have shown that this applies also to specific immune responses against various defined epitopes of the malaria antigens RESA (ring-infected erythrocyte surface antigen), MSA-1 (merozoite surface antigen 1), MSA-2, and antigens of the sporozoite and sexual stages [Sjöberg et al, 1992;Jepson et al 1997].…”

Section: Introductionmentioning

confidence: 99%

Heritability and segregation analysis of immune responses to specific malaria antigens in Papua New Guinea

et al. 1999

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Genetic regulation of immunoglobulin and specific antibody levels in twins reared apart.

Cited by 29 publications

References 12 publications

Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese male population

Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese male population

Thyroid peroxidase autoantibody epitopic ‘fingerprints’ in juvenile Hashimoto’s thyroiditis: evidence for conservation over time and in families

Heritability and segregation analysis of immune responses to specific malaria antigens in Papua New Guinea

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